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PATHOLOGY 


A    MANUAL    FOR    TEACHERS    AND 
STUDENTS 


BY 

W.  T.  COUNCILMAN,  M.D. 

SHATTUCK    PROFESSOR    07    PATHOLOGY,    HARVARD    11EDICAL    SCHOOL 


BOSTON 

.W.  M.  LEONARD,  PUBLISHER 
1912 


JBRARY 


COPYRIGHT,  1912, 
BY  W.  M.  LEONARD 


Stanhope  ipresa 

r.  H.  GILSON  COMPANY 
BOSTON.  U.S.A. 


C'tf 


Tms  WORK  is  AFFECTIONATELY  DEDICATED  TO  THE  MANY 

STUDENTS  OF  PATHOLOGY  FROM  ASSOCIATION 

WITH  WHOM  I  HAVE  DERIVED  THE 

GREATER  PROFIT 


PREFACE 

THIS  manual  has  developed  from  the  Syllabus  of  Pathology  pub- 
lished by  Councilman  and  Mallory  in  1904,  and  is  designed  with 
special  reference  to  the  teaching  of  the  subject.  The  work  gives 
the  plan  which  has  been  followed  in  teaching  pathology  in  the 
Harvard  Medical  School,  and  which  has  proven  to  be  successful. 
The  central  feature  is  that  opportunity  shall  be  given  the  student 
to  acquire  knowledge  of  the  subject  by  the  exercise  of  his  own 
powers.  To  this  end  laboratory  work  embracing  the  study  of  the 
gross  and  the  microscopic  changes  in  the  tissues  and  organs  and 
the  alterations  in  function  produced  by  disease,  is  made  the  main 
feature.  This  work  is  supplemented  by  lectures  which  have  the 
object  not  of  conveying  new  information,  but  of  expanding  and  co- 
ordinating the  knowledge  which  the  student  himself  has  acquired. 

Illustrations  were  purposely  omitted  hi  the  work.  Excellent 
and  accurate  as  are  most  of  the  illustrations  in  the  current  text- 
books of  Pathology,  they  still,  when  objective,  represent  areas 
carefully  selected  for  the  illustration  of  a  point,  more  commonly 
being  the  author's  interpretations.  It  is  much  better  that  the 
student  should  make  his  own  illustrations  from  the  objects  studied. 
Drawing  is  a  mode  of  expression  too  often  neglected.  It  helps 
enormously  in  accuracy  of  observation,  and  by  a  drawing  the  stu- 
dent often  can  convey  his  conception  of  an  object  more  clearly 
than  by  writing.  Blank  leaves  are  inserted  after  the  various 
chapters,  on  which  the  student  should  make  notes  of  conditions 
observed,  and  illustrate  these  with  original  drawings.  In  this  way 
he  will  contribute  to  the  creation  of  a  book  which  will  be  of  value 
to  him,  the  most  valuable  portion  being  his  own  contribution. 

In  the  text  there  is  considerable  difference  in  the  fullness  with 
which  the  various  subjects  have  been  treated.  This  is  particularly 
true  in  regard  to  the  treatment  of  the  infectious  diseases  and  the 
special  pathology  of  organs.  The  thorough  treatment  of  certain 
subjects  and  the  small  allowance  given  to  others  is  not  meant  as  an 
index  of  their  relative  importance,  but  the  fuller  description  is 
given  to  those  conditions  which  illustrate  principles  of  wide  appli- 

ii 


12  PREFACE 

cation.  The  work  does  not  aim  at  completeness;  at  present  no 
treatise  on  pathology  to  be  used  as  a  textbook  can  have  such  an 
object.  The  absence  of  any  save  indirect  consideration  of  the 
pathology  of  the  central  nervous  system  and  of  the  skin  is  con- 
spicuous. At  various  places,  both  in  the  general  text  and  in  the 
autopsies,  there  are  numerous  references  to  the  pathology  of 
these  organs,  and  their  pathology  is  usually  fully  considered  in 
the  special  teaching.  The  same  is  true  of  other  organs  of  which 
there  is  scant  mention.  The  student  must  supplement  the  text 
by  reading,  which  includes  to  as  large  an  extent  as  possible  the 
original  work  both  of  the  past  and  present,  on  which  the  concep- 
tions of  processes  as  given  are  based.  The  limitation  of  space  has 
prevented  the  discussion  of  controversial  points.  The  views  given 
are  the  personal  views  of  the  author  and  in  most  cases  are  those 
which  are  prevalent.  Opportunity  is  given  the  student  to  test  the 
conceptions  of  processes  given  and  to  amend  them  should  they  seem 
not  to  agree  with  his  observations. 

The  protocols  of  autopsies  added  to  the  various  chapters  will  be 
found  a  valuable  addition  in  impressing  on  the  mind  the  fact  that 
in  disease  it  is  the  organism  and  not  merely  the  organ  which  is 
affected.  Particularly  in  the  study  of  special  pathology  the  student 
is  likely  to  think  of  a  diseased  liver  or  kidney  as  an  isolated  product 
rather  than  of  the  individual  in  whom  there  is  a  diseased  organ. 
The  inter-relation  of  disease  in  the  individual  can  be  studied  in  no 
other  way  than  by  the  complete  autopsy.  There  is  sufficient  space 
for  the  addition  of  the  protocols  of  autopsies,  which  the  student 
sees  and  assists  in,  with  the  histological  descriptions  of  lesions. 
The  illustrative  autopsies  have  been  taken  from  those  filed  in  the 
Department  of  Pathology,  and  represent  the  work  of  many  men 
who  have  been  associated  with  the  department  and  who  have  in 
this  way  materially  assisted  in  the  work.  These  protocols  have  been 
used  with  but  little  change  and  correction  and  represent  consider- 
able variation  in  the  thoroughness  with  which  the  work  was  done 
and  in  accuracy  and  completeness  of  description. 

The  description  of  the  experiments  to  be  undertaken  in  connec- 
tion with  the  work  was  written  by  Assistant  Professor  Karsner, 
to  whom  I  am  indebted  also  for  reading  and  revising  the  manu- 
script. No  course  in  pathology  can  be  considered  at  all  ade- 
quate which  does  not  include  experimental  work  of  the  character 


PREFACE  13 

suggested  here.  These  are  to  be  carried  out  by  groups  of  students 
working  under  direct  supervision  and  the  description  of  the  ex- 
periments and  the  inferences  to  be  drawn  from  them  written  in 
the  blank  pages. 

The  value  of  experimental  work  on  the  part  of  the  students  is 
great,  not  only  because  of  the  training  in  the  experimental  method, 
but  particularly  because  of  the  correlation  between  cause  and  effect 
and  the  living  demonstration  of  altered  function.  The  proper 
point  of  view  is  attained  only  by  the  actual  participation  of  the 
student  in  the  work,  for  here  is  the  true  field  for  the  extension  of 
laboratory  study.  It  must  continually  be  borne  in  mind,  however, 
that  the  highest  ideal  of  humanity  must  be  striven  for,  not  in  the 
mere  observance  of  specified  rules  in  regard  to  anaesthesia  and  pain- 
less termination  of  experiments,  but  also  in  following  the  spirit  of 
these  rules  and  the  practice  of  kindness  and  gentleness. 


TABLE  OF  CONTENTS 

PAGE 
INTRODUCTION  WITH  CONSIDERATION  or  TISSUES 17-25 

ATROPHY^ 26-28 

DEGENERATIONS:  Cloudy  Swelling;  Fatty  Metamorphosis;  Glycogenic 
degeneration;  Mucoid  degeneration;  Amyloid  degeneration;  Hydropic 
degeneration;  Hyalin  degeneration;  Colloid  degeneration;  Calcifica- 
tion; Calculi;  Concretions;  Incrustations;  Pigmentation;  Death  and 
Necrosis;  Experiments 29-45 

INFLAMMATION:  Vascular  phenomena;  Exudation  and  the  Exudate;  Healing 
and  Repair;  Phagocytosis;  Granulation  tissue  formation  and  cicatriza- 
tion; Experiments 46-59 

THE  BLOOD:  Anaemia;   Haemolysis;   Plethora;   Hydraemia;   Coagulation; 

Thrombosis;  Embolism;  Experiments 60-70 

PATHOLOGICAL  ANATOMY  OP  HEART  AND  BLOOD  VESSELS:  Pericardium; 
Myocardium;  Heart  Hypertrophy;  Endocardium;  Veins;  Varicose 
veins;  Arteries;  Arteriosclerosis;  Syphilitic  arteriosclerosis;  Endar- 
teritis  obliterans;  Aneurysm 71-83 

PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION:  Pericardial  pressure; 
Valvular  Stenosis  and  Insufficiency;  Cardiac  Hypertrophy  and  Dilata- 
tion; Myocarditis;  Passive  congestion  of  lungs,  liver,  spleen,  kidneys, 
intestinal  canal,  brain;  Arteriosclerosis;  Haemorrhage;  (Edema; 
Experiments;  Autopsies 84-123 

GROWTH,  HYPERTROPHY,  HYPERPLASIA,  REGENERATION,  METAPLASIA....     124-130 

TUMORS:   General  Pathology:  Metastases;   Origins;   Cell  Characteristics; 

Inheritance;  ^Etiology;  Classification;  Cysts 131-148 

Special  Pathology:  Fibroma;  Papilloma;  Intracanalicular Tumors; 
Myxoma;  Lipoma;  Chondroma;  Osteoma;  Leiomyoma;  Haemangioma; 
Lymphangioma;  Endothelioma;  Sarcoma;  Neuroma;  Glioma;  Rhabdo- 
myoma;  Lymphoma;  Myeloma;  Chloroma;  Leukemia-Lymphatic; 
Leukaemia  Myelogenous;  Adenoma;  Adenocystoma;  Carcinoma; 
Chorio-epithelioma;  Hypernephroma;  Epidermoid  Cysts;  Cholesto- 
atoma;  Dermoid  Cysts;  Experiments;  Autopsies 140-193 

INFECTIOUS  DISEASES:  Infectious  Organisms  —  Bacteria;  Infection  from 
Surfaces;  Wound  Infection;  Phagocytosis;  Opsonins;  Bacteriolysis; 
Natural  Immunity;  Susceptibility;  Individual,  etc.:  Interaction  be- 
tween Tissues  and  Infectious  Organisms;  Atrium  of  Infection;  Periods 


16  TABLE  OF  CONTENTS 

PACK 

of  Disease;   Antitoxic  Action;   Germinal  Infection;   Secondary  Infec- 
tion; Experiments 194-209 

Special  Infections  —  Staphylococcus  Pyogenes  Aureus;  Strepto- 
coccus Pyogenes;  Diplococcus  pneumoniae;  Diplococcus  Intracellularis 
Meningitidis:  Gonococcus;  Bacillus  Tuberculosis;  Leprosy  Bacillus;  Tre- 
ponema  Pallidum;  Streptothrix  Actinomyces;  Bacillus  Mallei;  Bacillus 
Anthracis;  Bacillus  Diphtheriae;  Bacillus  Influenza;  Bacillus  Tetani; 
Bacillus  Pestis;  Bacillus  of  Soft  Chancre;  Bacillus  Typhosus;  Bacillus 
Dysenterise;  Spirillum  Choleras  Asiaticae;  Bacillus  Coli  Communis; 
Entamceba  Histolytica;  Plasmodium  Malariae;  Small  Pox;  Acute 
Anterior  Poliomyelitis 210-330 

PARASITIC  WORMS:  Cestodes  (Cysticerci) ;  Nematodes;  Distomata;  Experi- 
ments       33I-33S 

SPECIAL  PATHOLOGY  OF  ORGANS:     General  Considerations  applying  to 

Systemic  Disease. 336 

PATHOLOGY  or  THE  KIDNEY 337-364 

PATHOLOGY  OF  THE  ALIMENTARY  CANAL 365-371 

PATHOLOGY  OF  THE  PANCREAS 372-377 

PATHOLOGY  OF  THE  LIVER 378-389 

PATHOLOGY  OF  THE  LUNGS 390-393 


INTRODUCTION 

PATHOLOGY  is  the  study  of  disease.     Disease  may  be  defined  as 
a  change  produced  in  organisms  in  consequence  of  which  they  are 
no  longer  in  harmony  with  their  environment.     The  matter  which 
composes  the  living  organism  is  complex.     It  is  able  to  receive 
potential  energy  and  to  transform  it  into  those  forms  of  manifest 
energy,  which,  considered  together,  are  called  the  phenomena  of 
life.     The  elementary  substances  which  enter  into  living  matter  are 
known,  and  further,  it  is  known  that  these  elements  are  combined 
to  form  a  large  number  of  chemical  substances  most  of  which  are 
characterized  by  high  molecular  weights,  but  of  which  the  inter- 
molecular  arrangement,  the  chemical  structure,  is  unknown.    Nor 
is  much  known  concerning  the  structure  of  living  material  or  proto- 
plasm.   The  most  generally  accepted  theory  of  structure  is  that  of 
network  or  foam  structure  with  interstices  filled  with  material 
which  differs  in  its  physical  character  from  that  of  the  network. 
The  living  matter  is  heterogeneous  and  not  homogeneous,  and  in 
the  heterogeneous  mass  independent  chemical  processes  can  take 
place,  the  various  spheres  of  action  being  probably  separated  from 
one  another  by  colloid  walls.     Such  a  foam  structure  is  not  identical 
with  the  intracellular  reticulum  which  can  be  demonstrated  by 
certain  histological  methods  and  which  is  probably  an  artefact.    To 
such  a  conception  of  structure  the  objection  has  been  raised,  that 
solid  substances  pass  readily  from  one  part  of  a  cell  to  another; 
but  this  could  take  place  with  the  presence  of  a  reticulum  of  colloidal 
character.    By  microscopical  and  micro-chemical  observation  it  is 
possible  to  detect  various  substances  within  cells  the  chemical 
nature  of  some  of  which  is  known.    Under  pathological  conditions 
new  substances  may  be  found  or  those  normally  present  may  be 
increased  or  diminished  or  variously  altered. 

Living  matter  differs  from  dead  not  only  in  complexity  of  struc- 
ture, but  in  variability  of  structure  to  which  a  variability  in  re- 
action is  due  which  constitutes  the  individuality  of  the  organism. 
Such  individuality  is  not  found  in  non-living  substances,  in  which, 
under  uniform  conditions,  the  reactions  are  identical.  It  results 

17 


1 8  PATHOLOGY 

naturally  from  this,  that  disease  is  always  individual.  Neither  the 
lesions  nor  the  phenomena  are  precisely  the  same  in  each  instance, 
and  the  knowledge  on  which  measures  for  relief  are  based  must  come 
from  the  investigation  of  the  individual  case. 

Living  matter  is  adaptable.  An  organism  can  so  adapt  itself  to 
changing  conditions  that  the  phenomena  exhibited  are  the  usual. 
Within  the  species  there  is  variation  in  the  capacity  for  adaptation 
as  exhibited  by  different  individuals,  and  there  is  little  doubt  that 
such  variations  can  be  inherited.  When  the  conditions  acting  upon 
an  organism  are  beyond  the  range  of  adaptation,  a  change  is  pro- 
duced in  it  and  its  reactions  are  unusual.  The  organism  is  then 
diseased  and  the  condition  which  brought  about  the  change  is  a 
cause  of  disease.  Any  condition  acting  upon  an  organism  to  the 
action  of  which  the  organism  cannot  adapt  itself,  that  is,  cannot  in 
this  new  environment  exhibit  the  usual  phenomena,  is  a  cause  of 
disease. 

To  pathology  there  belongs  first  the  study  of  the  changes  in  the 
organism  to  which  the  abnormal  reactions  are  due.  These  changes 
are  called  lesions.  They  vary  greatly  in  character  and  extent,  may 
be  so  marked  as  to  be  easily  apparent  to  sight  and  touch,  or  only 
apparent  on  microscopical  or  chemical  examination.  It  is  possible 
for  changes  to  be  produced  in  cells  which  can  be  recognized  by 
abnormal  reactions  only,  there  being  no  alteration  apparent  by 
either  microscopical  or  chemical  investigation.  The  red  corpuscles 
of  an  animal  which  are  immunized  against  the  haemolytic  action  of 
a  foreign  serum  show  no  change  and  yet  they  are  so  altered  as  to 
resist  the  disintegration  which  takes  place  hi  the  corpuscles  of  the 
non-immune  animal  under  the  same  condition. 

The  study  must  further  embrace  the  cause  and  the  mode  of  de- 
velopment and  the  association  of  lesions.  In  so  complex  an  organ- 
ism as  man  with  complete  co-ordination  of  the  activities  of  each 
part,  the  inter-relation  of  lesions  is  most  important.  Pathology 
forces  upon  us  the  realization  that  the  body  is  an  organism,  not  a 
collection  of  independent  entities,  and  that  while  a  disease  may 
seemingly  be  localized  in  a  part,  yet  through  the  changed  condition 
of  that  part  the  entire  organism  is  diseased. 

The  study  of  the  lesions  alone,  even  though  the  steps  in  their 
evolution  could  be  traced  by  a  long  series  of  cases,  would  not  lead 
to  a  complete  comprehension  of  disease.  The  present  conception  of 


INTRODUCTION  19 

disease  is  due  mainly  to  the  knowledge  of  the  causes  of  disease  which 
has  come  in  the  last  forty  years.  This  knowledge  has  been  obtained 
chiefly  by  the  use  of  the  experimental  method  in  investigation  to  a 
greater  extent  than  ever  before,  a  method  which  has  revolutionized 
the  older  conception  of  the  cause,  development  and  processes  of 
disease;  has  correlated  these  processes  and  phenomena  with  their 
underlying  lesions  and  has  made  more  rational  the  classification 
and  nomenclature  of  disease.  The  same  cause  acting  in  the  same 
body  under  different  conditions  may  produce  lesions  which  anatom- 
ically may  differ  widely.  The  best  example  of  this  is  given  by 
tuberculosis.  The  discovery  of  the  bacillus  tuberculosis  and  the 
experimental  study  of  the  disease  have  made  it  possible  to  group 
together  such  conditions  as  Pott's  disease,  caseous  pneumonia, 
scrofula  and  miliary  tuberculosis. 

Pathology  is  to  be  looked  upon  as  one  of  the  divisions  of  biological 
science,  and,  as  such,  demands  close  and  patient  observation.  The 
student  must  approach  the  subject  of  disease  from  all  possible 
points  of  view,  utilizing  gross  anatomical,  histo-pathological,  and 
the  various  experimental  methods  of  study.  To  ensure  accuracy 
of  study  careful  record  of  all  work  should  be  made  both  by  objective 
description  and  careful  drawing,  the  latter  being  of  especial  advan- 
tage in  formulating  clear  conceptions.  By  mentally  combining  the 
information  acquired  in  these  various  ways  there  can  be  built  up  a 
knowledge  of  disease  that  will  serve  as  a  safe  guide  for  the  institu- 
tion of  means  to  prevent  disease  and  of  therapeutic  measures  to 
relieve  the  diseased  individual. 

The  study  of  pathology  presupposes  a  knowledge  of  normal 
structure  and  function.  In  the  study  of  normal  structure  the 
emphasis  is  properly  laid  on  the  architecture  of  organs,  the  inter- 
relations of  the  cells  and  tissues  composing  them  and  the  mode  of 
construction.  While  the  importance  of  this  is  true  in  the  study  of 
pathology,  yet  of  more  fundamental  importance  is  the  study  of  the 
material  which  enters  into  the  architectural  structure.  There  are 
certain  general  conceptions  of  tissue  which  it  is  important  to  hold 
in  mind  in  the  study  of  all  lesions. 

The  body  is  composed  of  an  external  surface  covered  by  epi- 
thelium which  surface  is  enormously  increased  by  glands  which 
belong  to  it  and  an  internal  surface,  also  covered  by  epithelium 
and  with  a  still  greater  duplication  of  surface  to  form  glands. 


20  PATHOLOGY 

These  surfaces  are  connected  at  the  mouth  and  the  anus.  The 
internal  surface  constitutes  the  alimentary  canal  and  the  respira- 
tory system.  There  is  also  a  third  epithelial  surface,  the  genito- 
urinary system  which  is  connected  with  the  external  surface  by  a 
single  opening.  These  surfaces  all  enclose  a  cavity  which  is  filled 
with  a  fluid  which  comes  into  close  relation  with  all  living  parts.  It 
is  only  by  means  of  such  a  physical  environment  that  nutrition  and 
the  necessary  interchange  between  the  living  matter  and  its  environ- 
ment can  take  place.  This  cavity  is  closely  packed  with  cells  and 
with  the  intercellular  substances  and  contains  large  spaces  or  fis- 
sures, of  which  the  peritoneal  space  is  an  example. 

CELLS  AND  INTERCELLULAR  SUBSTANCES.  It  is  customary  to 
think  of  the  cells  of  the  body  as  alone  possessing  the  structure  and 
qualities  by  which  living  matter  is  recognized.  The  intercellular 
substances  possess  some,  but  not  all  of  these  qualities. 

BLOOD  AND  LYMPHATIC  VESSELS.  Aside  from  the  highly  dif- 
ferentiated organs,  there  are  certain  cells  and  structures  which  are 
found  everywhere  and  which  must  be  considered.  The  blood 
vessels  are  best  thought  of  as  a  continuous  tube  lined  with  flat 
endothelial  cells  to  which  in  different  parts  other  elements  are 
added.  The  simple  endothelial  tube  is  represented  by  the  capil- 
laries. These,  unless  artificially  injected  or  filled  with  blood 
corpuscles,  are  not  easily  visible.  The  differentiation  of  the  endo- 
thelial tube  into  the  artery  takes  place  by  the  formation  outside  of 
the  endothelium  of  nonstriated  muscle  cells,  these  appearing  first 
as  single  separated  fibres,  which,  by  increase  in  number,  form  a 
continuous  band.  Elastic  tissue  is  formed,  represented  in  the 
smaller  arteries  by  a  band,  —  the  internal  elastic  lamina,  - 
immediately  outside  of  the  endothelium,  in  the  larger  by  elastic 
fibres  either  singly  or  in  bands  among  and  between  the  muscle 
fibres.  The  relative  amounts  of  muscle  and  elastic  tissue  differ 
both  according  to  size  and  function  of  the  arteries.  The  larger 
arteries  and  those  which  serve  mainly  the  purpose  of  conduction 
have  relatively  a  much  greater  amount  of  elastic  tissue  than  the 
smaller  and  distributing  arteries.  The  larger  arteries  have  a 
rather  indefinite  coat  of  connective  tissue  outside  of  the  media,  the 
adventitia,  which  bears  the  vasa-vasorum  and  connects  the  thick 
media  with  the  surrounding  tissue.  On  the  inside  of  the  media  a 
varying  amount  of  connective  tissue  is  found,  which,  with  the  endo- 


INTRODUCTION  21 

thelial  lining,  is  known  as  the  intima.  From  the  capillaries  the 
differentiation  into  veins  consists  in  the  formation  of  a  definite 
connective  tissue  coat  outside  of  the  endothelium,  and  in  the  larger 
veins  a  considerable  amount  of  muscular  tissue,  not  in  the  form  of 
a  definite  coat  as  in  the  arteries,  but  as  bands  of  muscle  fibres 
enclosed  in  the  connective  tissue.  With  this  there  is  a  small 
amount  of  elastic  tissue.  In  the  lung  there  is  so  little  difference 
in  structure  between  the  arteries  and  the  veins  that  they  are  best 
differentiated  by  their  position  in  reference  to  the  bronchi.  The 
lymphatic  vessels  form  a  system  of  simple  endothelial  tubes  ex- 
cept in  the  case  of  the  larger  lymph  trunks  in  which  the  wall  con- 
tains also  connective  tissue  and  muscle  fibres.  The  endothelial 
cells  of  the  lymphatic  vessels  are  larger  and  their  borders  more 
irregular  than  the  similar  cells  of  the  capillaries.  It  cannot  be 
regarded  as  absolutely  proven  whether  or  not  there  are  actual 
spaces  between  the  endothelial  cells.  Such  spaces  allowing  an 
actual  communication  between  the  tissue  fluids  and  the  contents 
of  the  lymphatics  seem  to  exist.  The  number  of  lymphatics  is 
greatly  underestimated;  they  cannot  be  recognized  in  sections  of 
tissues  unless  artificially  injected  or  filled  with  a  fluid  which  has 
been  coagulated  by  the  hardening. 

CONNECTIVE  TISSUE  consists  of  cells  and  intercellular  sub- 
stances in  fibrillar  form.  The  cells  vary  greatly  in  morphology  in 
different  parts  and  under  different  conditions.  The  cytoplasm 
usually  is  branched  peripherally,  the  nucleus  stains  lightly,  and  is 
usually  oval  or  elongated  in  shape.  In  the  cornea,  by  suitable 
stains,  a  beautiful  system  of  flat,  greatly  branching  cells  can  be 
demonstrated,  but  such  cells  cannot  be  taken  as  the  type  of  cells 
of  the  system  in  other  places.  Often  the  cells  in  sections  are 
represented  merely  by  a  rod-shaped  nucleus  in  close  association  with 
bands  of  fibres.  The  intercellular  substances  appear  in  the  form 
of  fibrils  which  show  certain  differences  in  form  and  in  their  chemi- 
cal reactions. 

WHITE  FIBROUS  TISSUE.  Connective  tissue  fibrils.  These  are 
delicate  fibrils  wavy  in  outline,  usually  to  a  greater  or  less  extent 
joined  closely  together  in  bundles,  this  arrangement  being  best 
marked  in  the  tendon,  or,  as  in  the  cornea,  they  may  be  arranged 
in  parallel  rows  forming  plates,  or,  as  in  the  subcutaneous  tissue, 
in  the  form  of  a  loose  mesh  work.  In  many  organs  the  connective 


22  PATHOLOGY 

tissue  takes  the  form  of  a  delicate  reticulum  of  closely  interwoven 
fibrils  which  form  an  internal  skeleton  of  the  organ.  Where  con- 
nective tissue  comes  in  contact  with  epithelium  the  fibres. are  often 
closely  united  to  form  a  definite  band,  the  membrana  propria. 
Among  these  fibres  there  are  larger,  denser  fibres  described  as 
fibroglia  fibres  which  have  a  close  relation  to  the  cells  and  which 
are  most  numerous  in  rapidly  growing  connective  tissue. 

ELASTIC  TISSUE  occurs  in  the  form  of  a  network  of  fibres  or  as 
thin  fenestrated  plates.  The  fibres  are  very  refractive  in  the 
fresh  state,  vary  greatly  in  size,  are  very  resistant  and  are  easily 
demonstrated  by  certain  methods  of  staining. 

There  are  also  fibrils  associated  with  epithelial  tissues.  These 
are  the  epithelial  fibrils  of  the  skin,  wavy  and  corkscrew  fibrils 
demonstrated  by  special  stains  which  pass  between  and  through 
the  epithelial  cells,  the  neurofibrils  and  neuroglia  of  the  central 
nervous  system  and  the  intracellular  fibrils  of  certain  epithelial 
organs.  The  neuroglia  of  the  central  nervous  system  is  very 
analogous  to  the  connective  tissue  both  in  normal  and  pathological 
conditions  and  like  it  consists  of  fibres  and  cells  in  more  or  less 
definite  relation  with  each  other.  The  fibrils  are  rarely  joined 
together  to  form  bands.  The  neuro-fibrils,  demonstrated  only  by 
special  methods  of  staining,  are  different  from  the  neuroglia  and 
are  more  directly  associated  with  the  ganglion  cells. 

THE  BLOOD  AND  THE  BLOOD  FORMING  TISSUES.  The  red  cells  in 
the  blood  contain  haemoglobin  which,  when  it  has  been  fixed  by 
hardening  agents,  stains  deeply  with  such  acid  dyes  as  eosin.  The 
haemoglobin  is  easily  dissolved  out  of  the  corpuscles  in  tissues  which 
have  not  been  properly  hardened  and  the  corpuscles  are  then  either 
invisible  or  appear  as  pale  rings.  Red  blood  corpuscles  can  be 
found  in  practically  every  section  of  tissue;  the  size  varies  but  little 
in  different  methods  of  hardening  and  they  form  a  good  basis  for 
comparative  measurement.  As  seen  in  sections  of  tissues  hardened 
in  Zenker's  fluid,  they  appear  somewhat  smaller  than  in  the  fresh 
blood  and  have  an  average  diameter  of  6/j.. 

Among  the  white  corpuscles  of  the  blood  can  be  distinguished 
the  polynuclear  leucocytes  which  form  70  to  72  per  cent  of  all  the 
leucocytes.  These  are  larger  than  the  red  corpuscles,  and  the 
contour  is  sharp,  giving  the  appearance  of  a  definite  membrane. 
The  cytoplasm  contains  fine  round  granules  which  are  often  lost  in 


INTRODUCTION  23 

the  process  of  hardening  and  which  take  a  double  stain  with  acid 
and  basic  dyes.  The  nucleus  consists  of  several  masses  connected 
together  by  fine  filaments,  the  whole  having  a  semicircular  or 
crescentic  form.  It  stains  intensely  with  basic  dyes. 

LYMPHOCYTES.  These  form  22  to  25  per  cent  of  the  white  cor- 
puscles. In  coverslip  preparations  of  blood  a  larger  and  smaller 
size  can  be  recognized,  the  smaller  greatly  predominating.  As  seen 
in  sections,  particularly  after  hardening  in  Zenker's  solution,  the 
differentiation  into  smaller  and  larger  cells  is  not  apparent.  They 
are  very  characteristic  cells  about  the  size  of  the  red  corpuscles; 
the  nucleus  is  round  and  stains  brightly,  the  chromatin  having 
chiefly  a  peripheral  arrangement,  the  masses  at  the  periphery  con- 
nected with  the  intranuclear  granules  by  a  chromatin  network. 
Only  a  small  and  irregular  amount  of  cytoplasm  is  visible.  This 
was  formerly  supposed  to  be  non-granular,  but  more  recently 
granules  of  a  definite  character  have  been  demonstrated. 

EOSINOPHILES.  These  form  2  to  4  per  cent  of  the  leucocytes. 
The  size  of  the  cell  and  the  characteristics  of  the  nucleus  is  the  same 
as  that  of  the  polynuclear  cell,  the  outline  is  definite,  the  cytoplasm 
contains  round  granules,  easily  preserved,  larger  than  the  neutro- 
phile  granules  and  which  stain  intensely  with  eosin. 

MAST  CELLS  form  about  0.5  per  cent  of  the  leucocytes.  The 
nucleus  varies  much  in  character  and  generally  is  polymorphous. 
The  cytoplasm  contains  numerous  fairly  coarse  granules  which 
stain  intensely  with  basic  dyes. 

LARGE  MONONUCLEAR  LEUCOCYTES  form  i  to  3  per  cent  of  the 
leucocytes.  They  are  the  largest  of  the  leucocytes,  the  nucleus 
lightly  stained,  oval,  usually  horseshoe  in  shape;  the  cytoplasm  is 
non-granular,  takes  no  definite  stain,  and  the  cell  outline  is  distinct. 

BLOOD  PLATELETS  are  round  or  irregular  small  masses  of  cyto- 
plasm, 2  to  3/z  in  diameter,  without  nuclei  and  with  large  indefinite 
granules.  They  easily  disintegrate  and  are  not  frequently  found  in 
sections  of  tissue  in  a  recognized  form  but  appear  as  large  masses 
of  indefinite  granular  appearance  within  blood  vessels. 

The  intercellular  substance  of  the  blood,  the  blood  plasma,  is 
a  fluid  of  complex  composition.  It  contains  7.26  per  cent  of 
protein  which  is  composed  of  serum  albumen  4.01  per  cent;  of  para- 
globulin  2.83  per  cent;  fibrinogen  0.42  per  cent.  It  contains 
further  numerous  extractives,  salts  and  enzymes. 


24  '  PATHOLOGY 

Under  normal  conditions  the  red  corpuscles,  polynuclear  leu- 
cocytes, the  lymphocytes  and  mast  cells  are  formed  in  post  foetal  life 
in  the  bone  marrow  exclusively.  They  arise  by  a  process  of  dif- 
ferentiation from  cells  of  an  embryonic  type  in  the  marrow,  only  the 
completely  differentiated  cells  which  have  no  further  power  of  multi- 
plication entering  the  blood.  Under  pathological  conditions  blood 
formation  can  take  place  in  other  organs,  notably  in  the  spleen. 

The  lymphoid  cells  of  the  blood  are  produced  in  the  lymphoid 
tissue.  This  tissue  is  found  chiefly  in  the  form  of  lymph  nodes 
which  are  aggregates  of  lymphoid  cells  enclosed  in  a  capsule.  The 
cells  are  enclosed  in  a  reticulum  and  are  arranged  into  masses  and 
strands  by  means  of  a  network  of  channels  which  connect  with  the 
lymphatic  vessels  entering  and  leaving  the  nodes.  Cell  production 
takes  place  in  the  germinal  centres  of  the  nodes  which  are  composed 
of  large  cells  with  an  oval  vesicular  nucleus  and  a  visible  cyto- 
plasm. In  the  germinal  centres  nuclear  figures  commonly  are 
found.  The  channels  or  sinuses  are  in  close  relation  to  the  cells 
in  the  follicles  and  contain  a  wide-meshed  reticulum  which,  with  the 
walls  of  the  sinuses,  is  covered  with  endothelial  cells.  In  addition 
to  the  definite  nodes  small  masses  of  lymphoid  tissue  not  enclosed 
in  definite  capsules  are  found  in  numerous  places.  In  the  intestinal 
canal  between  the  epithelium  and  the  muscularis  mucosa  there  is  a 
form  of  lymphoid  tissue  which  differs  in  some  respects  from  that  in 
the  lymph  nodes.  Cells  formed  in  the  nodes  pass  into  the  sinuses 
and  thence  by  means  of  the  efferent  lymph  vessels  into  the  general 
lymph  stream  and  the  blood. 

There  is  much  doubt  about  the  origin  of  the  large  mononuclear 
cells  of  the  blood.  They  are  distinguished  from  the  other  blood  cells 
not  only  by  form  and  structure,  but  also  by  function,  in  that  they 
alone  of  the  leucocytes  are  phagocytic  for  other  cells,  particularly 
for  the  lymphocytes.  Cells  of  similar  character  may  be  found  as 
free  cells  hi  the  tissue  and  in  the  sinuses  of  the  lymph  nodes 
where  they  undoubtedly  are  formed  from  the  lining  endothelial 
cells. 

NERVES.  With  the  other  structures  which  have  been  described 
will  be  found  nerves.  Those  in  the  form  of  medulated  fibres  in 
bundles  can  easily  be  recognized  by  the  sections  of  the  sheath  of 
Schwann  forming  in  cross  or  oblique  sections  circles  or  ovals  en- 
closing the  axis  cylinders.  Non-medulated  fibres  even  in  the  form 


INTRODUCTION  25 

of  bundles  of  sympathetic  fibres  are  not  easily  recognized  without 
special  modes  of  staining. 

The  highly  differentiated  tissues  such  as  muscle,  bone,  etc.,  need 
not  be  considered  here. 

TISSUE  FLUIDS.  All  the  structures  which  have  been  mentioned 
are  impregnated  with  or  surrounded  by  the  tissue  fluid.  The 
contents  of  the  blood  and  lymphatics  are  separated  from  the  tissue 
fluids  by  thin  protoplasmic  membranes,  possibly  containing  minute 
spaces  at  the  line  of  juncture  of  the  cells  composing  them.  Such 
walls  are  osmotic,  filtering  membranes,  and  the  thin,  probably 
colloidal,  walls  allow  cells  and,  to  some  extent,  probably  other  solid 
substances  to  pass  through  without  rupture.  The  flow  of  the  blood 
is  towards  the  tissues,  that  of  the  lymphatics  away  from  the  tissues. 
The  tissue  fluid  receives  constant  addition  from  the  blood,  and  it  is 
constantly  depleted  by  the  lymph  outflow.  Both  interchanges 
take  place  through  membranes  and  neither  the  blood  fluid  nor  the 
lymph  can  be  taken  as  representing  the  tissue  fluid.  Soluble  sub- 
stances can  diffuse  through  it  and  it  is  not  impossible  that  there  are 
movements  and  currents  in  it.  It  also  contains  cells  which  are  the 
free  cells  of  the  tissue  and  in  pathological  conditions  these  cells  can 
be  increased  in  number  and  other  cells  added  to  them,  such  as 
polynuclear  leucocytes,  large  mononuclear  cells  or  endothelial  cells 
and  lymphoid  cells.  By  means  of  the  tissue  fluid  all  cell  inter- 
change takes  place,  by  it  all  substances,  whether  simply  nutritive 
or  toxic,  are  brought  to  the  cells  and  all  products  of  secretion  and 
metabolism  removed. 


25  b 


25  c 


25  d 


25  e 


25  g 


25  h 


ATROPHY 

By  atrophy  is  understood  a  decrease  in  size,  with  or  without  a 
numerical  decrease,  in  the  cells  or  essential  tissue  of  an  organ.  The 
condition  usually  is  followed  by  a  diminution  in  the  gross  size  and 
weight.  Exception  to  this  may  be  found  as  in  emphysema  of  the 
lungs,  where  there  is  a  great  reduction  in  the  amount  of  lung  tissue, 
but  owing  to  the  accompanying  dilatation  of  the  air  spaces  the  lung 
may  be  increased  in  size.  In  certain  forms  of  muscle  atrophy  there 
may  be  extensive  formation  of  fat  between  the  atrophied  muscle 
fibres  and  both  size  and  weight  of  the  muscles  increased.  The 
condition  of  atrophy  is  to  be  distinguished  from  that  of  hypoplasia, 
in  which  there  is  defective  development  or  growth.  Atrophic  organs 
are  rather  firmer  and  tougher  than  normal,  for  the  connective  tissue 
does  not  undergo  atrophy  to  the  same  degree  as  the  parenchym- 
atous  cells,  and  may  even  increase  in  amount.  There  usually  is 
also  an  increased  depth  of  color  as  in  brown  atrophy  of  the  heart. 
The  tissue  changes  in  atrophy  vary  greatly.  In  atrophy  of  fat  the 
fat  globules  within  the  cells  are  broken  up  and  the  cells  either 
disappear  or  return  to  an  undifferentiated  condition,  or  the  tissue 
fluid  may  be  increased,  forming  a  gelatinous  oedema.  In  atrophy- 
ing muscles  there  may  be  a  large  increase  in  the  number  of  the 
sarcolemma  nuclei.  Atrophy  may  be  associated  with  various 
degenerations  particularly  fatty  degeneration.  A  distinction  be- 
tween active  and  passive  atrophy  is  to  be  made,  the  former  a 
primary  change  in  the  cells  which  diminishes  their  nutrition,  the 
latter  an  atrophy  due  to  deficient  food  supply.  According  to  the 
cause  the  following  forms  of  atrophy  may  be  distinguished. 

PHYSIOLOGICAL  ATROPHY.  The  atrophy  which  certain  organs 
undergo  at  age  periods,  as  the  atrophy  of  the  thymus,  the  atrophy 
of  the  ovaries  at  the  menopause,  etc. 

ATROPHY  FROM  MALNUTRITION.  This  includes  both  atrophy 
from  deficiency  of  food,  and  atrophy  in  consequence  of  defective 
blood  supply.  In  starvation  all  the  tissues  atrophy  in  varying 
degree,  the  loss  being  most  marked  in  the  fat  and  muscular  tissue. 

26 


ATROPHY  27 

PRESSURE  ATROPHY.  In  this  there  probably  is  the  combined 
action  of  the  effect  of  pressure  exerted  on  the  blood  vessels  interfering 
with  nutrition  and  direct  effect  of  pressure  on  the  cells.  The  best 
example  of  atrophy  from  pressure  is  given  in  the  deep  furrow  ;  cross 
the  liver  produced  by  constriction  of  the  waist.  The  atrophy  of  the 
kidney  in  hydronephrosis  is  due  in  part  at  least  to  the  interference 
with  the  circulation  in  consequence  of  the  increased  pelvic  and 
intratubular  pressure. 

ATROPHY  FROM  DISUSE.  There  is  a  close  relation  between  the 
nutrition  and  function  of  tissues,  and  disuse  results  in  atrophy. 
There  is  a  slower  circulation  in  inactive  organs  and  the  functional 
intracellular  changes  seem  to  be  essential  for  the  nutritive  activity. 
The  atrophy  of  an  immobilized  fractured  extremity  is  an  example. 

NEUROPATHIC  ATROPHY.  Atrophy  may  be  seen  in  parts  in  which 
the  normal  nerve  supply  has  been  interrupted  or  impaired.  The 
causal  relation  here  is  complicated,  for  there  usually  is  interference 
with  the  circulation  in  consequence  of  the  loss  of  vaso-motor 
activity,  impairment  of  function  and  the  action  of  trauma  due  to 
loss  of  sensation.  Whether  or  not  the  nerves  affect  the  nutrition 
of  cells  independently  of  the  conditions  which  necessarily  accom- 
pany loss  of  nerve  supply  has  never  been  satisfactorily  determined. 

SENILE  ATROPHY.  Atrophy  is  the  most  important  of  the  phe- 
nomena of  age.  It  is  seen  in  the  loss  of  hair  and  teeth,  in  the 
thinning  of  the  corium,  in  the  weakening  of  the  supporting  tissues 
giving  greater  effect  to  gravity,  in  the  evidence  of  diminution  in 
function  of  all  organs  and  in  loss  of  weight,  of  individual  organs. 
The  loss  of  weight  of  the  entire  body  is  not  so  apparent  owing  to 
the  frequent  tendency  to  fat  formation.  The  reserve  force  is 
diminished ;  fife  is  carried  on  with  the  full  use  of  all  the  force  of  the 
body,  and  is  so  ordered  as  to  make  the  least  demands  on  function. 
Senile  atrophy  is  complex  in  its  causes  and  modes  of  production. 
The  atrophy  affects  different  organs  in  different  degree  and  shows 
in  individuals  great  variation  in  situation,  in  degree  and  in  progress. 
All  the  causes  of  atrophy  are  associated  in  senile  atrophy.  Mal- 
nutrition due  to  diseases  of  the  blood  vessels  plays  an  important 
part.  To  this  must  be  added  the  effect  of  organic  disease  with  the 
necessary  impairment  of  function.  In  the  regular  course  of  life, 
slight  injuries  of  organs  are  constantly  being  produced,  which  are 
in  part  repaired  and  in  part  remain,  and  are  compensated  for  by 


28  PATHOLOGY 

greater  activity  in  other  parts.  In  advancing  age  there  is  ex- 
perienced the  effect  of  the  sum  of  injuries,  together  with  a  di- 
minished power  of  repair,  and  diminution  in  the  reserve  power  of 
function.  In  addition  certain  tissues  of  the  body,  such  as  arterial 
walls,  seem  to  wear  out  in  the  course  of  time,  perfectly  normal 
arteries  being  rare  after  the  age  of  forty.  So  constant  are  these 
vascular  lesions  that  they  seem  almost  sufficient  in  themselves  to 
explain  the  senile  atrophy.  Even  the  diminution  in  power  of 
regeneration  and  repair  is  certainly  in  part  due  to  the  difficulty  of 
provision  of  increased  vascularity  arising  from  disease  of  the  vessels. 
But  apart  from  the  action  of  these  conditions,  there  is  probably  in 
other  organs  something  of  the  same  change  which  is  seen  in  arteries 
but  is  less  manifest.  Animals  which  are  but  little  or  not  at  all  the 
subject  of  senile  arterial  change  show  senile  changes  much  the  same 
as  those  which  occur  in  man. 


DEGENERATIONS 

Certain  changes  which  the  cells  and  tissues  of  the  body  undergo 
in  consequence  of  the  action  of  injurious  conditions  are  classed 
together  as  degenerations.  Degeneration  may  affect  both  the  cells 
and  the  intercellular  substances;  in  certain  cases  it  is  most  marked 
in  a  single  organ,  in  others  more  generally  distributed. 

CLOUDY  SWELLING  is  the  most  common  of  the  degenerations.  It 
is  produced  by  the  action  of  toxins  as  in  the  acute  infectious  diseases 
results  from  insufficient  blood  supply  as  in  high-grade  anaemia  and 
may  be  produced  experimentally  by  subjecting  the  tissues  to  the 
action  of  a  variety  of  injurious  agents  as,  for  example,  cantharadin. 
Microscopically,  the  affected  organs  are  slightly  increased  in  size, 
paler  and  more  opaque  than  normal.  The  appearance  has  been 
aptly  compared  to  that  presented  by  tissues  which  have  been 
boiled.  When  examined  fresh,  the  cells  are  more  granular  than 
normal,  the  granulation  often  obscuring  the  nucleus.  The  granules 
disappear  on  the  addition  of  acetic  acid  or  caustic  potash.  The 
condition  is  best  studied  in  the  epithelial  cells  of  the  kidney  and 
liver  and  in  the  muscle  cells  of  the  heart.  Sections  of  the  kidney 
show  the  cells,  particularly  those  of  the  convoluted  tubules,  swollen, 
the  edges  often  broken  and  irregular,  the  striated  border  partly  or 
wholly  absent,  the  cell  granules  irregular  in  size  and  arrangement, 
and  usually  vacuolation  of  the  protoplasm.  There  is  no  evidence 
of  an  increase  in  the  amount  of  cell  material.  The  change  seems  to 
consist  in  an  increase  in  the  amount  of  intracellular  fluid  with  the 
precipitation  in  granular  form  of  substances  previously  in  solution. 
It  is  indicative  of  a  minor  degree  of  injury  from  which  the  cell  can 
recover. 

FATTY  METAMORPHOSIS.  Fat  in  the  form  of  neutral  fat  is  con- 
tained in  most  of  the  tissues  of  the  body.  In  certain  organs,  as  in 
the  kidney  of  man,  it  can  be  demonstrated  only  by  chemical 
methods.  This  is  so  either  because  it  is  in  some  way  combined 
with  the  protein  of  the  cell  or  is  present  in  granules  so  fine  as  to  be 
invisible  microscopically.  Fat  is  found  chiefly  in  the  fat  depots 

of  the  body  and  in  the  liver.    Almost  invariably  some  fat  is  found 

29 


30  PATHOLOGY 

in  the  liver  and  the  amount  here  can  be  greatly  increased  so  that 
the  excess  represents  a  pathological  condition.  In  consequence 
of  a  diet  rich  in  fats  or  carbohydrates,  abnormally  large  quantities  of 
fat  may  be  brought  to  the  liver  and  stored  there,  or  in  consequence 
of  conditions  which  interfere  with  oxidation  processes  the  stored 
fat  is  not  consumed.  The  liver  cells  can  contain  fat  in  such  large 
amounts  as  to  resemble  fat  cells.  Such  fat  is  found  chiefly  in  the 
periphery  of  the  lobules,  and  may  exist  without  any  evidence  of 
other  alteration  in  the  cell  than  diminution  of  the  cytoplasm.  In 
certain  organs,  as  in  the  heart,  the  increase  of  the  normal  fat  tissue 
may  constitute  an  injury.  The  normal  fat  of  the  pericardium  can  be 
very  greatly  increased  and  even,  particularly  in  the  right  ventricle, 
grow  into  the  myocardium  separating  the  fibres.  The  mass  of 
inert  tissue  here  increases  the  work  of  the  heart  and  the  fat  sub- 
stituted for  myocardium  does  not  so  well  resist  intracardiac  pres- 
sure. In  organs  which  have  undergone  atrophy  large  amounts  of 
fat  may  be  formed,  replacing  the  atrophied  tissue  as  in  muscles  long 
in  disuse.  All  these  forms  of  fat  formation  are  called  fatty  infiltra- 
tion. By  fatty  degeneration  is  meant  the  appearance  of  fat  in 
association  with  cell  degeneration.  Such  fatty  degeneration  may 
produce  but  little  alteration  in  the  appearance  of  the  tissue  to  the 
naked  eye,  particularly  when  it  is  diffusely  distributed.  The 
alterations  are  much  more  evident  when  the  degeneration  is  focal. 
The  fat  in  fatty  degeneration  may  be  merely  the  normal  fat  pre- 
viously combined  with  protein,  and,  owing  to  change  in  the  cell, 
separated  from  this  combination;  or  it  may  be  fat  which  is  brought 
to  the  cell  from  without  and  which  the  cell,  owing  to  degeneration, 
cannot  metabolize.  The  old  view  that  the  fat  is  formed  directly 
from  the  protein  of  the  cell  is  no  longer  held.  In  fatty  degeneration 
the  fat  usually  is  in  the  form  of  small  granules  which  can  be  dis- 
tinguished in  fresh  tissues  by  their  refraction  and  by  their  persis- 
tence after  the  addition  of  strong  acetic  acid.  After  most  methods 
of  hardening,  the  fat  is  dissolved  by  the  alcohol.  The  best  method 
of  demonstration  is  by  staining  with  Scharlach  R  frozen  section  of 
organs  which  have  been  hardened  in  formalin.  The  fat  in  the  cells 
varies  in  amount  from  a  few  granules  to  a  seeming  substitution  of  all 
of  the  cytoplasm  by  fat.  Connective  tissue  cells  may  appear,  when 
stained,  as  branched  granular  masses.  The  cells  show  other 
changes  in  addition  to  the  fat,  and  often  the  fat  seems  merely  an 


DEGENERATIONS  31 

addition  to,  or  further  progress  of,  cloudy  swelling.  In  tissues  in 
which  there  is  extensive  fatty  degeneration,  the  fat  may  be  present 
in  the  intercellular  substances  also,  appearing  in  the  form  of  a  very 
fine  emulsion.  In  such  cases  it  is  not  certain  whether  the  emulsion 
is  in  the  tissue  fluid  and  results  from  the  destruction  of  fatty  de- 
generated cells,  or  whether  there  is  an  actual  formation  of  fat  in  the 
fibrils.  The  amount  of  fat  often  seems  too  great  to  be  of  cell  origin. 
The  presence  of  fat  in  the  endothelial  cells  of  vessels  is  an  important 
means  of  recognizing  early  degeneration.  In  degeneration  of 
nervous  tissues  fat  is  formed  from  the  myelin.  Where  tissue  con- 
taining fat  undergoes  solution  in  the  body  setting  the  fat  free,  large 
phagocytic  cells  which  take  up  the  fat  are  constant.  These  are 
known. as  compound  granule  cells,  or,  from  their  discoverer,  as 
Gliiges  corpuscles.  Fatty  degeneration  is  a  common  lesion  in  the 
body;  it  may  be  produced  by  the  action  of  many  poisons,  by  con- 
ditions of  anaemia  both  local  and  general  and  by  most  of  the  bac- 
terial infections.  Fat  crystals  occasionally  are  found  free  in  the 
cells  or  tissues.  Needle-shaped  crystals  of  fatty  acids  may  be  found 
within  necrotic  fat  cells,  in  decomposed  pus,  in  gangrenous  tissue 
and  in  tissue  in  which  there  is  extensive  fatty  degeneration.  Choles- 
trin  is  found  under  somewhat  the  same  conditions,  but  has  not  the 
same  relation  to  decomposition.  It  appears  in  tissues  as  character- 
istic, flat  rhomboidal  plates,  where  there  is  slow  destruction  of  cells 
and  where  the  circulation  is  imperfect,  and  in  fluids  where  patho- 
logical secretions  or  exudations  are  long  retained.  It  also  forms  one 
of  the  most  important  constituents  of  biliary  calculi.  In  fluids  its 
presence  can  be  recognized  by  the  naked  eye  by  the  refractive 
glistening  scales.  As  tissues  ordinarily  are  hardened  cholestrin  is 
dissolved  by  the  alcohol  leaving  narrow  fissures  in  the  walls  of  which 
foreign  body  giant  cells  may  be  present. 

GLYCOGENIC  DEGENERATION.  Glycogen  normally  is  found  in 
certain  tissues  of  the  body,  particularly  in  the  liver,  muscle  and 
cartilage.  It  is  readily  soluble  in  water  and  for  its  detection,  tissues 
should  be  hardened  in  absolute  alcohol  and  stained  with  iodine 
which  colors  the  glycogen  brown.  It  is  found  in  abundance  in  some 
of  the  tumors,  in  the  leucocytes  in  certain  inflammatory  exudations 
and  in  the  cells  of  most  organs  in  diabetes.  It  occurs  in  the  cells 
only  and  in  the  form  of  granules,  globules,  or  irregular  masses. 
Rarely,  it  may  be  found  in  the  nuclei.  In  diabetes  glycogen  is 


32  PATHOLOGY 

found  in  large  amounts  in  the  cells  of  Henle's  loops  constituting  a 
characteristic  lesion. 

MUCOID  DEGENERATION.  Mucin  normally  is  found  as  a  secre- 
tion of  the  epithelial  cells,  particularly  the  cylindrical  cells  of  the 
intestinal  villi  and  in  the  interstices  of  connective  tissue,  especially 
of  tendon.  It  is  a  glassy,  viscid  substance,  dissolves  readily  in 
weak  alkaline  solutions  and  is  precipitated  by  acetic  acid.  It  is 
more  abundant  in  foetal  than  in  adult  tissue,  the  umbilical  cord  being 
the  type  of  connective  tissue  containing  a  large  amount  of  mucin. 
In  hardened  tissues  it  may  be  recognized  by  its  staining  with  basic 
dyes.  It  has  its  chief  importance  in  connection  with  tumors,  where 
it  often  is  found  in  large  amounts.  In  addition  to  its  presence  in 
tumors  it  is  formed  in  increased  amounts  in  degenerative  conditions 
of  the  connective  tissue  especially  in  association  with  defective 
nutrition.  It  may  be  formed  in  greatly  increased  amounts  in  the 
intestinal  epithelium.  There  are  a  number  of  substances  termed 
pseudomucins  which  have  the  physical  characteristics  of  mucin  but 
differ  from  it  in  reaction. 

AMYLOID  DEGENERATION.  Amyloid  is  a  homogeneous,  firm  sub- 
stance, never  found  in  normal  tissues  and  occurs  pathologically  not 
in  cells  but  as  an  infiltration  of  the  intercellular  tissue.  Chemically, 
it  is  a  protein  compound  of  condroitin-sulphuric  acid  and  gives  a 
characteristic  stain  both  with  iodine  and  with  methyl  violet.  With 
iodine  it  stains  mahogany  brown  and  with  the  methyl  violet  a  rose 
pink.  It  occurs  in  conditions  of  chronic  disease  such  as  tuber- 
culosis, long  standing  suppurations  especially  those  connected  with 
bone  and  very  commonly  is  found  in  old  cases  of  syphilis.  The 
organs  which  are  the  seat  of  amyloid  deposits,  usually  are  enlarged, 
of  firm  consistency  and  pale  with  a  peculiar  waxy  refraction.  It 
occurs  by  predelection  in  certain  organs,  the  order  being  spleen,  liver, 
kidneys,  adrenal  glands,  mucous  membrane  of  intestine  and  the 
lymph  nodes.  Of  all  the  tissues  of  the  body  the  small  arteries  are 
most  frequently  affected.  Here  it  occurs  in  the  muscular  coat  at 
first  as  masses  surrounding  and  finally  supplanting  the  muscle 
fibres.  It  has  never  been  found  in  the  blood  nor  is  it  deposited  on 
the  inner  wall  of  blood  vessels.  The  general  conclusion  is  that  it  is 
formed  in  the  tissues  these  supplying  the  protein  which  unites  with 
condroitin-sulphuric  acid  contained  in  the  blood.  Occasionally 
rather  ill-defined  crystallization  is  seen  in  amyloid  and  this  is  more 


DEGENERATIONS  33 

common  in  the  amyloid  of  lower  animals,  particularly  the  mouse. 
The  presence  of  amyloid  in  tissue  is  associated  always  with  atrophy 
and  other  forms  of  degeneration,  due  principally  to  the  interference 
with  nutrition  occasioned  by  the  amyloid  masses  around  the  vessels. 
It  is  uncertain  whether  or  not  amyloid  ever  disappears  from  the 
tissue. 

In  the  spleen  amyloid  may  appear  only  in  the  media  of  the 
arteries  or  as  an  infiltration  around  the  fibres  of  the  reticulum  of  the 
follicles  or  as  a  more  diffuse  infiltration  of  the  pulp. 

In  the  liver  amyloid  appears  first  around  the  arteries,  then  around 
the  capillaries  in  the  middle  zone  of  the  lobule,  and  in  advanced 
cases  large  areas  may  be  entirely  converted  into  amyloid;  the  cells 
first  become  atrophic  and  then  wholly  disappear. 

In  the  kidney  amyloid  may  affect  the  straight  vessels  of  the  pyra- 
mids or  the  glomerular  arteries  and  the  glomeruli.  In  the  glomeruli 
it  appears  first  in  the  capillary  wall  and  finally  all  the  vessels  may 
be  obliterated. 

In  the  intestinal  wall  the  infiltration  often  is  confined  to  the 
vessels  of  the  villi.  On  pouring  iodine  over  the  surface  the  villi 
appear  as  a  brown  pile. 

In  lymph  nodes  the  amyloid  appears  first  in  the  follicles  and 
the  entire  node  may  be  converted  into  it. 

LOCAL  AMYLOID  FORMATIONS.  In  addition  to  the  general  amy- 
loid degeneration  and  not  associated  with  the  causes  which  produce 
it,  there  may  be  local  formations  of  amyloid  in  the  tissues.  The 
amyloid  appears  in  the  form  of  tumor-like  swellings  at  the  base  of 
the  tongue  in  the  mucous  membrane  of  larynx  and  trachea,  and  in 
the  eyelids.  It  has  been  supposed  that  the  amyloid  here  may  be 
due  to  an  excessive  local  production  of  condroitin  sulphuric  acid. 
(See  case  of  amyloid  degeneration,  page  267.) 

HYDROPIC  OR  VACUOLAR  DEGENERATION.  In  this  condition 
vacuoles  filled  with  fluid  appear  in  the  cells,  usually  without  other 
evidence  of  degeneration.  It  is  seen  most  commonly  in  the  cells 
in  dropsy.  It  may  be  found  in  the  striated  muscles  and  in  the 
epithelium.  Occasionally  filaments  of  fibrin  may  be  demonstrated 
in  the  vacuoles. 

HYALIN  DEGENERATION.  This  includes  those  forms  of  degen- 
eration, both  in  the  cells  and  in  the  intercellular  substances,  in 
which  hyalin  masses  with  no  distinguishing  chemical  characteristics 


34  PATHOLOGY 

are  formed.  In  general,  these  masses  are  homogeneous,  rather 
refractive  and  have  an  affinity  for  acid  stains.  There  probably  are 
a  number  of  different  substances  included  under  this  head.  From 
its  physical  characteristics  amyloid  would  have  been  so  included; 
it  has,  however,  distinguishing  chemical  characteristics.  Hyalin 
masses  are  formed,  as  thrombi,  within  blood  vessels  (page  63). 
Hyalin  may  appear  also  in  walls  of  vessels  in  the  same  position  as 
amyloid.  Irregular  hyalin  masses  may  form  on  the  outside  of 
capillaries  particularly  those  of  the  brain.  Such  masses  stain  with 
haematoxylin  and  may  appear  as  strings  of  beads  along  the  vessels. 
In  the  lymph  nodes  small  reticular  areas  of  hyalin  may  be  formed 
about  the  capillaries.  Fibrin  in  old  exudations  may  be  converted 
into  hyalin  masses.  In  the  connective  tissue,  particularly  in  cica- 
trices, hyalin  material  may  be  deposited  between  the  fibrils  or  the 
fibrils  are  converted  into  it.  Occasionally  fresh  sections  of  such 
material  gives  a  slight  metachromatic  stain  with  methylene  blue. 
The  hyalin  in  the  corpora  fibrosa  of  the  ovary  results  from  the  con- 
version of  both  the  cells  and  the  intercellular  substance  into  hyalin. 
A  peculiar  form  of  hyalin  is  due  to  necrosis  of  striated  muscle  and  is 
known  as  Zenker's  degeneration.  In  this  condition  the  necrotic 
muscle  substance  is  converted  into  homogeneous,  highly  refractive 
material  broken  into  disks.  In  the  cells  hyalin  appears  in  the  form 
of  globules,  which,  in  some  cases,  stain  intensely  with  acid  fuchsin. 
These  frequently  are  found  in  tumor  cells,  in  the  cells  of  the  spleen, 
bone  marrow  and  in  the  mucosa  of  the  intestine.  In  the  kidney, 
especially  in  connection  with  amyloid  degeneration,  the  swollen 
epithelial  cells  of  the  proximal  convoluted  tubules  become  filled  with 
hyalin  globules;  these  on  rupture  of  the  cells  fuse  into  hyalin 
masses  which  later  appear  in  the  urine  as  highly  refractive,  so- 
called  waxy  casts.  The  tissue  of  tubercles  either  before  or  after 
caseation  may  become  converted  into  hyalin  and  the  same  is  true 
of  gummata. 

COLLOID  DEGENERATION.  The  term  colloid  is  given  to  thick 
glue-like  or  gelatinous  substances  which  are  formed  by  epithelial 
cells  and  has  reference  solely  to  the  physical  properties  of  the  sub- 
stances. Unfortunately,  the  type  of  such  substances  is  given  by 
the  material  in  the  alveoli  of  the  thyroid  gland  which  we  now  know 
to  be  a  substance  of  definite  chemical  composition,  and  has  no 
chemical  relation  to  other  colloid  substances  save  those  formed  in 


DEGENERATIONS  35 

the  hypophesis.  The  retained  secretion  of  cysts  particularly  of  the 
kidney  may  be  converted  into  colloid.  Colloid  is  not  deposited 
as  an  intercellular  substance. 

Corpora  amylacea  are  concentric  oval  or  circular  bodies  of  waxy 
character,  and  should  be  grouped  among  the  colloids.  The  name 
refers  to  the  supposed  relationship  to  amyloid  shown  by  their 
reaction  to  stains.  This  staining  reaction  varies  and  is  not  founded 
on  any  chemical  identity  with  amyloid.  These  bodies  are  found  in 
the  acini  of  the  prostate  in  both  normal  and  pathological  conditions. 
They  may  be  found  also  in  the  lungs,  in  the  ventricles  of  the  brain 
and  in  other  situations.  They  represent  a  product  of  epithelial 
secretion  and  are  resistant  to  the  action  of  acids  and  alkalies. 

CALCIFICATION.  Under  normal  conditions  the  deposit  of  lime 
salts  in  the  body  takes  place  only  in  the  matrix  of  bone.  Lime  is 
present  in  the  blood,  where  it  is  held  in  solution  by  the  colloids  and 
carbon  dioxide  and  exists  in  the  form  of  an  unstable  double  salt  of 
calcium  bicarbonate  and  dicalcium  phosphate.  Under  pathological 
conditions  lime  salts  are  deposited  only  in  tissues  which  are  necrotic 
or  have  undergone  some  form  of  degeneration.  The  deposit  of  lime 
salts  in  such  tissues  is  due  either  to  the  fact  that  in  consequence  of 
chemical  changes  in  the  tissue  the  lime  salts  can  no  longer  be  held 
in  solution,  or  the  degenerated  tissue  has  a  special  affinity  for  the 
lime,  in  this  respect  resembling  the  matrix  of  forming  bone.  Arteries 
which  have  undergone  degeneration  are  particularly  prone  to  calci- 
fication. Lime  is  readily  deposited  in  cicatricial  tissue  in  any  part 
of  the  body,  but  particularly  in  the  lungs.  Necrotic  tissue  in  the 
body,  whether  in  connection  with  organs  as  in  infarctions,  in  thrombi, 
in  caseous  material,  etc.,  or  as  retained  exudation,  readily  under- 
goes calcification.  The  tendency  to  calcification  may  be  increased 
by  the  addition  of  lime  to  the  food,  and  particularly  when  there  is 
absorption  of  lime,  as  in  cases  of  osteomalacia.  This  is  described  as 
lime  metastases  and  the  deposits  take  place  in  the  lungs,  stomach 
and  kidneys.  Lime  salts  may  enter  also  into  combination  with 
fatty  acids  when  these  are  formed  in  necrosis  of  fat  tissue,  in  which 
form  they  are  resistant  to  the  action  of  acids.  Necrotic  ganglion 
cells  may  become  infiltrated  with  lime  salts  and  completely  pre- 
serve their  form.  Tissue  which  is  undergoing  calcification,  and  the 
calcified  material  as  well,  stains  deeply  with  haematoxylin.  When 
the  calcifying  tissue  is  treated  with  nitrate  of  silver  and  exposed  to 


36  PATHOLOGY 

the  light,  the  silver  is  reduced  by  the  phosphate  of  lime  and  appears 
as  black  silver  phosphate. 

CALCULI,  CONCRETIONS,  INCRUSTATIONS.  Solid  substances  may 
be  deposited  in  the  cavities  or  canals  of  organs  or  upon  their  walls. 
In  the  latter  position  they  are  known  as  incrustations.  Such 
deposits  always  take  place  upon  or  within  some  substance  known 
as  a  nucleus  or  matrix  which  may  be  a  group  of  necrotic  cells,  a 
mass  of  mucus,  or  a  foreign  body  of  any  sort.  Usually  the  dis- 
solved substance  is  deposited  in  crystalline  form,  although  later  the 
crystalline  structure  may  disappear.  The  crystals  tend  to  be 
deposited  at  right  angles  to  the  surface  giving  a  radiate  structure. 
The  deposit,  moreover,  usually  takes  place  at  intervals;  the  surface 
may  become  covered  with  mucin  or  some  other  substance  and  a  new 
deposit  on  this  gives  in  addition  a  concentric,  laminated  structure. 
These  masses  may  give  rise  to  important  pathological  conditions 
by  the  injury  to  tissues  caused  by  their  presence,  and  by  the  ob- 
struction of  canals  and  ducts.  The  most  common  of  such  sub- 
stances are: 

Biliary  calculi  may  form  in  the  gall  bladder  or  bile  ducts  and 
usually  are  termed  gall  stones.  Cholestrin  forms  the  greater  part 
of  all  gall  stones  and  calcium  salts  of  the  bile  pigments  are  present 
also.  Other  substances  may  be  present  in  variable  amounts  and 
affect  the  color  and  other  physical  characteristics  of  the  calculi. 

Urinary  calculi  may  appear  in  the  urinary  bladder,  in  the  ureters, 
in  the  pelvis  and  calices  of  the  kidney.  According  to  the  character 
of  the  urine,  calculi  which  differ  in  appearance  and  chemical  com- 
position are  produced.  Uric  acid  calculi  are  the  most  common  and 
characteristic.  Phosphate  calculi  are  formed  as  a  result  of  decom- 
position in  the  urine,  with  formation  of  ammonia  from  the  urea. 
Such  calculi  may  form  upon  a  uric  acid  calculus,  this  by  the  irrita- 
tion and  injury  of  the  tissues  having  facilitated  decomposition. 
Calculi  of  this  sort  may  attain  large  size  and  in  the  kidney  may 
completely  fill  the  pelvis  and  calices.  Other  rare  urinary  calculi 
are  formed  of  calcium  oxylate,  of  xanthin  and  of  other  substances. 

Pancreatic  calculi  are  formed  in  the  pancreatic  duct  and  are 
composed  of  a  mixture  of  calcium  phosphate  and  carbonate  assocr 
ated  with  more  or  less  organic  matter. 

Salivary  calculi  formed  in  the  salivary  ducts  have  the  same  com- 
position as  the  pancreatic  calculi,  but  contain  more  organic  matter. 


DEGENERATIONS  37 

Intestinal  concretions  usually  have  a  nucleus  of  some  foreign 
substance  or  undigested  particles  of  food.  Such  concretions  are 
sometimes  found  in  the  vermiform  appendix. 

Preputial  concretions  may  form  beneath  the  unretracted  prepuce 
by  the  deposit  of  urinary  salts  in  the  retained  smegma. 

Lung  stones  may  be  concretions  formed  in  the  bronchi,  in  which 
they  appear  as  concentric  laminated  bodies,  or  may  be  portions  of 
calcined  lung  tissue  which  have  become  separated. 

Phleboliths  are  due  to  the  calcification  of  thrombi  and  not  in- 
frequently are  found  in  the  vessels  of  the  spleen. 

PIGMENTATION.  Both  the  normal  and  pathological  pigments  of 
the  body  can  be  divided  into  the  autochthonous,  those  formed  by  the 
metabolic  activity  of  the  cells;  the  hcematogenous,  those  derived 
from  the  hemoglobin  of  the  blood;  and  the  extraneous,  or  those 
introduced  into  the  body  from  without. 

Autochthonous  pigments.  The  best  known  of  these  is  the 
melanin  which  forms  the  coloring  matter  of  the  skin,  eyes  and  hair. 
It  may  be  increased  in  amount  from  exposure  to  sun  in  which  case 
it  may  be  diffusely  distributed,  or  appear  as  freckles.  It  is  in- 
creased also  in  pregnancy,  and  in  chronic  inflammation  of  the 
skin. 

Addison's  Disease  is  caused  by  destructive  disease  of  the  chro- 
mafine  system,  the  pigment  of  the  skin  and  of  the  mucous  mem- 
brane of  the  mouth  being  greatly  increased.  The  pigment  in  small 
brownish  granules  is  found  in  the  chromatophores  of  the  cori«m 
and  in  the  cells  of  the  Malpighian  layer.  The  pigment  is  generally 
supposed  to  be  melanin. 

Lipochrome  is  a  yellow  pigment  probably  a  fat  or  fat  compound, 
staining  with  Scharlach  R,  and  is  found  in  fat,  in  the  corpus  luteum, 
in  the  epithelium  of  the  seminal  vesicles,  in  the  testicle  and  epididy- 
mis,  and  in  the  ganglion  cells.  The  pigment  of  the  heart  and  kid- 
neys is  of  the  same  character  and  is  increased  in  senile  atrophy. 
In  the  heart  the  pigment  is  found  around  the  nuclei  and  extends 
longitudinally  in  the  fibre.  It  is  seen  also  in  chloroma. 

Ochronosis  is  the  name  given  to  a  condition  in  which  pigment 
related  to  or  identical  with  melanin  is  deposited  in  the  cartilages,  in 
the  capsules  of  joints  and  rarely  in  the  intima  of  vessels.  The 
disease  is  rare  and  the  origin  of  the  pigment  is  unknown. 

Malarial  pigment  is  formed  from  the  haemoglobin  of  the  blood 


38  PATHOLOGY 

corpuscles  by  the  parasite  of  the  disease.  It  is  intensely  black  and 
exists  in  the  parasite  in  the  form  of  small  rods.  It  is  set  free  when 
the  parasite  segments  and  is  taken  from  the  blood  by  the  phago- 
cytic  cells  of  the  liver  and  the  spleen,  producing  the  dark  brown  or 
black  color  of  these  organs  seen  in  malaria.  When  large  numbers 
of  the  parasites  containing  pigment  accumulate  within  the  capil- 
laries of  the  brain  cortex,  they  give  to  this  a  peculiar  chocolate 
brown  color.  The  pigment  remains  in  the  spleen  for  a  long  period 
after  recovery  from  the  infection. 

In  haemochromatosis  a  dark  brown  or  black  pigment  is  deposited 
in  the  cells  and  tissues  or  organs,  particularly  in  the  liver  and 
pancreas.  The  pigment  seems  to  be  of  two  sorts,  one  containing 
iron,  the  other  iron  free.  It  is  not  homogeneously  distributed  in 
the  organs,  but  is  found  in  association  with  the  areas  of  degenera- 
tion and  connective  tissue  increase  which  form  a  definite  feature  of 
the  disease.  This  is  the  pigment  seen  in  bronzed  diabetes. 

Haematogenous  pigments.  The  great  source  of  pigment  in  the 
body  is  the  haemoglobin  of  the  red  blood  corpuscles.  Haematin  is 
easily  separated  from  the  globin  and  divides  into  two  pigments, 
one,  haematoidin,  isomeric  with  bilirubin,  the  other,  haemosiderin, 
containing  the  iron  component  of  the  haematin.  When  haemorrhage 
takes  place  in  the  tissues  haemosiderin  is  formed  by  the  destruction 
of  red  corpuscles  within  phagocytic  cells,  and  appears  within  cells 
as  round  or  irregular  brown  masses  which  give  the  iron  reaction. 
The  haematoidin  is  usually  carried  to  the  liver  and  excreted  as 
biliverdin.  Where  the  haemorrhage  is  large  in  amount  and  where 
the  conditions  of  absorption  are  poor  and  oxygen  deficient,  red 
rhombic  plates  of  crystalized  hasmatoidin  are  found. 

Haemoglobin  may  be  set  free  in  the  blood  by  the  destruction  of 
the  red  corpuscles  producing  the  condition  of  haemoglobinaemia. 
The  haemoglobin  as  methaemoglobin  is  excreted  by  the  kidneys 
giving  to  the  urine  a  characteristic,  dark,  smoky  color.  The 
kidneys  have  a  peculiar  dark  brown  color,  and  the  haemoglobin  may 
be  found,  after  staining  with  eosin,  as  beaded  masses  in  the  epithe- 
lium of  the  convoluted  tubules,  and  in  the  form  of  tube  casts. 
When  the  destruction  of  blood  is  slow  and  continuous  as  in  per- 
nicious anaemia,  the  haemoglobin  is  broken  up,  forming  haemotoidin 
which  is  excreted  in  the  bile,  and  haemosiderin,  which  in  the  form 
of  brown  granules,  giving  the  iron  reaction,  is  found  in  the  liver, 


DEGENERATIONS  39 

kidneys  and  spleen.  In  the  liver  cells  these  granules  accumulate 
around  the  bile  capillaries. 

JAUNDICE  is  an  accumulation  of  the  coloring  matter  of  the  bile 
in  the  cells  and  tissues  of  the  body.  The  liver  being  the  only  place 
where  bile  is  formed,  jaundice  is  always  hepatogenous  in  origin,  and 
is  due  to  the  entry  of  bile  into  the  blood.  The  bile  finds  its  entry 
into  the  blood  in  two  ways;  (i)  in  consequence  of  obstruction  to  the 
outflow  brought  about  by  external  pressure  upon  the  ducts  or  the 
presence  within  them  of  obstructing  substances :  (2)  by  degenerative 
conditions  in  which  the  anatomical  relations  are  disturbed.  In 
infectious  diseases  in  which  there  has  been  increased  blood  destruc- 
tion, jaundice  may  come  on  rapidly  and  is  due  to  increased  forma- 
tion of  bile  combined  with  liver  degeneration.  The  bile  enters  into 
the  blood  through  the  lymphatics,  and  also  from  the  rupture  of 
the  bile  capillaries  into  the  sinusoids.  The  coloring  matter  of  the 
bile  diffuses  through  the  tissues  giving  them  a  diffuse  yellow  color, 
It  is  taken  up  from  the  blood  by  the  cells  of  certain  tissues,  as  the 
kidneys,  and  appears  in  these  as  greenish  yellow  granules.  The 
most  intense  pigmentation  is  found  in  the  liver.  The  liver  cells  do 
not  seem  to  contain  an  increased  amount  of  pigment.  The  bile 
capillaries  are  dilated  and  filled  with  thick  masses  of  pigment. 
Pigment  in  granular  form,  or  in  form  resembling  casts  of  the  capil- 
lary bile  ducts,  is  contained  also  in  the  endothelial  cells  of  the  vessels 
and  in  large  phagocytic  cells  within  the  sinusoids.  There  is  more 
pigment  in  the  centre  than  in  the  periphery  of  the  lobule.  In 
association  with  the  pigmentation  there  always  is  found  well- 
marked  fatty  degeneration  of  the  organs  due  probably  to  the  action 
of  the  bile  salts  which  are  absorped  with  the  bile  pigment. 

Extraneous  pigments.  The  most  common  of  these  is  carbon. 
This  is  inhaled  as  dust  and  is  deposited  partly  in  the  tissue  of  the 
lung  and  in  part  finds  its  way  into  the  lymphatics  and  is  deposited 
in  the  vessels,  in  the  tissue  about  them  and  in  the  peribronchial 
lymph  nodes.  When  the  amount  of  pigment  is  very  great,  as  in 
the  lungs  of  coal  miners,  the  pigment  may  also  find  its  way  into  the 
blood  and  be  deposited  in  the  liver  and  spleen.  By  means  of  tattoo- 
ing various  insoluble  pigments  are  introduced  into  the  tissues;  these 
in  part  remain  at  the  place  of  introduction,  in  part  are  carried  by 
the  lymphatics  into  the  adjacent  lymph  nodes.  Silver,  when  taken 
into  the  body  in  excess,  may  be  deposited  in  metallic  form  in  the 


40  PATHOLOGY 

skin,  intestine,  mesenteric  lymph  nodes  and  kidneys.  In  the  latter 
the  deposit  takes  place  in  the  walls  of  the  capillaries  of  the  glomeruli 
which  appear  grossly  as  black  points.  In  chronic  lead  poisoning 
the  lead  accumulates  in  the  tissues  in  solution;  the  blue  line  of  the 
gums  at  the  edge  of  the  teeth  is  due  to  the  formation  of  lead  sul- 
phide by  the  sulphuretted  hydrogen  formed  by  decomposition 
around  the  teeth. 

Other  crystalline  substances  may  be  deposited  in  the  tissues,  the 
most  conspicuous  example  of  which  is  given  by  the  needle-shaped 
crystals  of  sodium  urate  deposited  in  the  cartilage,  in  the  capsules 
of  the  joints,  often  in  the  connective  tissue  about  them,  and  which 
give  rise  to  marked  inflammatory  reactions. 


DEATH  AND   NECROSIS 

DEATH  OF  THE  BODY  AS  A  WHOLE  results  at  once  from  the  cessa- 
tion of  the  functions  of  the  nervous  system,  or  of  the  heart,  or  of  the 
lungs.  There  are  other  organs  of  the  body,  such  as  alimentary 
canal,  kidney,  liver  and  adrenal  glands,  whose  function  is  essential 
for  life,  but  death  does  not  take  place  immediately  on  the  cessation 
of  their  function.  In  death  of  the  individual  all  parts  do  not  die  at 
once;  the  muscles  and  nerves  may  react  to  stimulation  and  the 
function  of  the  glands  and  cardiac  contraction  may  be  excited  for  as 
long  as  several  hours  after  death.  Certain  cells,  such  as  the 
epidermis,  may  be  preserved  for  days  or  months  and  under  proper 
conditions  will  grow. 

With  the  cessation  of  life  the  body  is  subject  to  the  unmodified 
action  of  the  physical  environment. 

There  is  no  further  heat  production  after  death  and  the  body 
takes  the  temperature  of  the  surrounding  medium.  This  loss  of 
heat  is  called  algor  mortis.  The  only  exception  to  this  is  after 
death  from  sunstroke  and  from  certain  acute  infections  of  the 
nervous  system  in  which  there  may  be  marked  production  of  heat 
for  several  hours  after  death. 

Rigor  mortis  takes  place  usually  within  twelve  hours  after  death; 
it  is  a  contraction  and  hardening  of  the  muscles  due  to  some  change 
in  their  physico-chemical  relation.  It  begins  in  the  muscles  of  the 
head,  extends  to  the  extremities  and  usually  disappears  in  about 
twenty-four  hours.  It  varies  in  the  time  of  onset,  in  degree  and 
duration.  It  is  most  intense  and  most  rapid  in  its  appearance  in 
death  preceded  by  active  muscular  exercise,  for  example,  in  death 
from  violence.  After  death  from  slow  wasting  diseases,  it  may  be 
slight  and  of  short  duration. 

The  blood,  while  it  remains  fluid,  obeys  the  laws  of  gravity  and 
settles  in  the  most  dependent  parts,  producing  a  homogeneous  or 
mottled  bluish-red  discoloration  called  livor  mortis.  Parts  of  the 
body  subject  to  pressure  are  white  and  bloodless.  The  blood  later 
becomes  laked  and  the  diffused  haemoglobin  stains  the  vessels  and 
the  surrounding  tissue.  Laking  takes  place  more  quickly  under  the 
influence  of  bacterial  action. 

41 


42  PATHOLOGY 

The  blood  coagulates;  this  is  more  noticeable  where  it  is  in 
large  masses  as  in  the  great  vessels  and  in  the  heart.  The  charac- 
ter of  the  clot  depends  upon  the  rapidity  with  which  coagulation 
takes  place.  It  may  be  red  when  the  coagulation  has  been  so  rapid 
that  the  red  corpuscles  have  not  had  time  to  settle  by  gravity,  or 
white  and  red  when  the  process  has  been  slower.  Such  post  mortem 
clots  can  be  distinguished  from  thrombi  by  their  greater  trans- 
parency and  by  the  fact  that  they  do  not  adhere  to  the  walls  of  the 
vessels. 

The  body  also  loses  its  moisture  by  evaporation.  Drying  of  the 
surface  takes  place  where  the  epidermis  is  thin  as  on  the  cornea, 
and  from  areas  where  the  epidermis  is  absent. 

Decomposition  and  putrefaction  of  the  body  due  to  bacterial 
action  takes  place.  The  bacteria  are  present  in  the  alimentary 
canal,  from  this  they  make  their  way  into  the  dead  tissue  and 
various  changes  follow.  There  is  an  almost  characteristic  odor; 
gas  may  form  in  the  organs  due  to  the  action  of  the  bacillus  aerogenes 
capsulatus.  A  greenish  discoloration  appears  which  is  usually 
diffuse  over  the  abdominal  organs  and  in  the  form  of  lines  along 
the  vessels.  The  relations  between  tissues  and  tissue  fluids  may  be 
altered  leading  to  the  more  easy  separation  of  tissues.  The  epi- 
dermis, for  instance,  may  be  removed  in  large  flakes.  The  rapidity 
with  which  decomposition  takes  place  varies,  and  is  dependent 
upon  many  factors,  such  as  temperature,  the  cause  of  death,  etc. 
Ferments  which  were  present  in  the  body  may  act  upon  the  tissues. 
When  gastric  juice  is  present  in  the  stomach  it  may  act  upon  the 
wall  in  the  most  dependent  portion,  producing  softening  and  even 
perforation.  If  the  gastric  juice  enters  the  lungs  it  may  soften  this 
tissue  so  that  pathological  conditions  may  be  simulated. 

In  the  microscopic  examination  of  tissues  it  is  important  to  know 
what  post  mortem  changes  take  place  in  the  cells.  The  finer  details 
of  histological  structures  are  quickly  lost  in  decomposition,  cell 
outlines  are  obscured  or  broken,  the  nuclei  either  do  not  stain,  or 
the  chromatin  swells  up  and  the  nucleus  stains  diffusely.  Changes 
take  place  most  quickly  in  the  parenchymatous  organs  and  par- 
ticularly in  the  central  nervous  system.  The  muscles  and  connec- 
tive tissue  membranes  preserve  their  characteristics  much  longer. 

NECROSIS  is  local  death  of  tissue  in  continuity  with  living  tissue 
and  subject  to  the  action  of  the  circulation  and  the  tissue  fluids. 


DEATH  AND  NECROSIS  43 

Under  these  conditions  cells  undergo  changes  which  differ  from 
those  due  to  post  mortem  decomposition.  When  necrosis  is 
brought  about  by  some  agent  which  coagulates  the  tissue  and  pre- 
vents the  action  of  intra-  or  extracellular  ferments,  the  usual 
changes  associated  with  necrosis  do  not  occur.  The  epithelial  cells 
of  the  stomach  may  be  killed  when  carbolic  acid  is  swallowed,  but 
no  histological  change  is  found  in  them.  The  changes  in  the  cells 
by  which  necrosis  may  be  recognized  affect  both  the  nucleus  and 
cytoplasm.  Those  in  the  nucleus  are  karyolysis,  karyorhexis  and 
pyknosis. 

Karyolysis  means  disappearance  of  the  nucleus  by  solution  and 
diffusion  of  the  nuclear  material.  Karyorhexis  means  a  disturbance 
of  the  normal  distribution  of  the  chromatin  in  the  nucleus  so  that 
it  swells  up  into  clump-like  masses;  or  the  entire  nucleus  may  be 
filled  with  swollen  homogeneous  chromatin.  In  pyknosis  the 
chromatin  is  converted  into  small  irregular  masses  which  stain 
intensely  with  basic  stains  and  which  are  distributed  in  the  cells 
or  as  detritus  in  the  surrounding  tissue  fluid.  Pyknosis  occurs 
especially  in  leucocytes.  The  nuclear  detritus  of  lymphocytes 
tends  to  take  crescentic  shapes.  Normal  granulation  and  all 
structural  differentiation  in  the  cytoplasm  disappears.  The  cell 
becomes  changed  into  a  homogeneous,  highly  refractive  mass  often 
containing  vacuoles  which  may  contain  filaments  of  fibrin.  The 
necrotic  cells  usually  are  swollen,  and  separated  from  their  connec- 
tion with  one  another.  The  cytoplasm  has  an  increased  affinity  for 
acid  stains.  The  necrosis  may  affect  areas  of  tissue  or  only  certain 
groups  of  cells;  in  the  liver,  for  instance,  affecting  the  liver  cells 
of  an  area  leaving  the  endothelial  cells  unchanged  or  it  may  affect 
single  liver  cells  irregularly  distributed. 

COAGULATION  NECROSIS.  Under  this  name  a  special  form  of 
necrosis  has  been  described  as  a  coagulation  of  the  cytoplasm  and 
the  tissue  fluids  with  or  without  the  formation  of  fibrin.  The  type 
of  this  form  of  necrosis  is  seen  in  infarction.  It  is  doubtful  if  this 
should  be  regarded  as  a  special  type  of  necrosis  since  in  all  necrosis 
coagulation  of  the  cell  contents  probably  takes  place. 

LIQUEFACTION  OF  COLLIQUATION  NECROSIS.  The  necrotic  tissue 
may  become  liquefied  and  form  a  space  filled  with  fluid  and  tissue 
detritus.  This  occurs  chiefly  in  the  brain. 

FAT  NECROSIS.    This  is  a  peculiar  form  of  necrosis  which  is  due 


44  PATHOLOGY 

to  the  action  of  the  pancreatic  juice  on  the  surrounding  fat  tissue. 
This  juice  contains  a  fat-splitting  ferment,  which  separates  the 
fatty  acids  from  the  glycerine.  The  acids  remain  as  needle-shaped 
crystals  or  combine  with  the  lime  salts  to  form  soaps. 

Certain  forms  of  necrosis  may  be  associated  with  a  definite  cause. 
In  eclampsia,  for  instance,  areas  of  necrosis  are  produced  in  the 
liver  which  consist  in  a  peculiar  fibrinoid  change  of  the  cells. 

The  causes  of  necrosis  are  manifold.  The  two  most  general 
causes  which  are  met  with  in  human  pathology  are  disturbances 
in  the  circulation  and  the  action  of  toxic  substances  which  usually 
are  of  bacterial  origin. 

GANGRENE  is  necrosis  with  putrefaction.  Necrosis  of  large 
external  parts  of  the  body,  as  an  extremity,  in  many  ways  resembles 
general  death.  The  changes  of  the  cells  and  tissues  seen  in  focal 
necrosis  are  not  present,  and  the  parts  are  subjected  more  to  the 
action  of  certain  physical  changes,  for  example,  evaporation.  The 
most  frequent  cause  of  this  necrosis  is  loss  of  blood  supply  by  occlu- 
sion of  vessels;  other  causes  which  injure  tissue  in  mass,  as  the 
action  of  cold,  may  produce  it.  The  putrefactive  bacteria  may  be 
present  in  the  necrotic  tissue  or  they  quickly  gain  access  to  it  and 
putrefaction  takes  place.  Two  main  forms  of  gangrene  are  dis- 
tinguished. The  first  is  dry  gangrene,  in  which  there  is  rapid  loss 
of  fluid  by  evaporation  and  the  tissue  becomes  dry  and  black, 
resembling  that  of  a  mummy.  In  the  other  form,  known  as  moist 
gangrene,  there  is  a  greater  abundance  of  fluid  in  the  part  and  the 
putrefactive  processes  more  marked.  This  form  of  gangrene  takes 
place  in  cedematous  parts  or  when,  during  the  process  of  necrosis, 
an  exudation  is  formed  in  the  tissue,  or  when,  owing  to  the  presence 
of  a  large  amount  of  subcutaneous  fat,  evaporation  is  interfered 
with.  When  necrosis  takes  place  in  parts  of  the  body  where  there 
is  abundant  moisture  and  a  ready  access  for  bacteria,  as  in  the  lung, 
putrefaction  resulting  in  gangrene  is  likely  to  occur. 

EXPERIMENTS.  For  the  experimental  study  of  degenerations, 
cloudy  swelling  and  fatty  degeneration  are  most  adaptable.  Cloudy 
swelling  can  be  produced  by  injecting  o.ooi  gram  cantharadin,  dis- 
solved in  acetic  ether,  subcutaneously  into  a  guinea  pig  daily  for 
three  days.  Histological  sections  and  salt  solution  suspensions  of 
fresh  scrapings  from  the  liver  and  kidneys  present  instructive  pic- 
tures. Fatty  degeneration  can  be  produced  in  the  cat  or  dog  by 


DEATH  AND  NECROSIS  45 

administration,  through  the  stomach  tube,  of  phosphorus  in  olive  oil 
in  doses  of  0.020  gram  to  the  kilogram  of  body  weight.  Frozen 
sections  and  scrapings  of  liver  can  be  stained  with  Scharlach  R. 
and  studied.  The  histological  appearance  is  striking  and  constant. 

Calcification  is  best  produced  experimentally  by  the  ligation, 
aseptically  and  under  ether  anaesthesia,  of  the  renal  artery  of  a 
rabbit.  Autopsy  at  the  end  of  four  weeks  shows  the  organ  shrunken, 
extensively  calcified  and  occasionally  partly  ossified.  Necrosis 
and  connective  tissue  growth  are  marked  and  the  deposition  of  the 
calcium  salts  in  the  renal  tubules  is  clearly  made  out  on  histological 
examination.  An  additional  experiment  in  the  so-called  metastatic 
calcification  is  made  by  the  injection  of  10  c.c.  saturated  calcium 
lactate  solution  into  the  peritoneal  cavity  of  a  rabbit.  Stomach 
and  lungs  show  the  metastatic  deposit  of  the  precipitated  lime. 

Of  great  interest  in  pigmentation  is  the  phagocytosis  and  trans- 
ference of  the  pigment  granules.  Five  cubic  centimetres  of  finely 
divided  cinnibar  suspension  are  injected  into  the  peritoneum  and 
in  various  subcutaneous  positions.  Autopsy  and  microscopic 
sections  twenty-four  hours  later  show  beautifully  the  phagocytosis 
and  distribution  of  pigment  in  the  regional  lymphatic  apparatus. 
Biliary  pigmentation  of  the  liver  and  other  tissues  can  be  demon- 
strated by  the  ligation  of  the  common  duct  of  the  cat  or  rabbit, 
preferably  the  former.  The  liver  shows  diffuse  pigmentation  as 
well  as  focal  accumulation  of  granules. 

For  the  experimental  phases  of  necrosis  the  student  is  referred 
to  the  effect  of  the  ligation  of  the  renal  artery  of  the  rabbit.  A 
most  striking  example  is  seen  in  the  liver  of  guinea  pigs  which  have 
been  subjected  to  prolonged  chloroform  anaesthesia.  This  can  be 
done  successfully  by  placing  the  animals  in  a  box  with  a  glass  cover 
and  forcing  the  chloroform  vapor  in  by  means  of  compressed  air. 
An  outlet  is  placed  at  the  opposite  end  of  the  box  to  provide  for 
the  free  passage  of  the  vapor  and  the  animals  observed  through 
the  glass  cover.  Repetition  on  two  or  three  successive  days  ensures 
the  success  of  the  experiment  and  if  the  animals  are  killed  at  differ- 
ent periods  the  rapidity  of  regeneration  can  be  followed.  Ether 
necrosis  (see  page  129)  and  specific  immune  serum  necrosis  (see  page 
69)  will  be  studied  later. 


45 


45  b 


45 


454 


45  e 


45  f 


45  g 


45  h 


45  i 


45  J 


45k 


451 


45  m 


45  n 


45  P 


INFLAMMATION 

This  term  is  used  to  express  the  sum  of  the  changes  which  take 
place  in  a  tissue  after  an  injury.  The  changes  vary  both  in  degree 
and  character;  they  are  affected  by  the  nature  of  the  injurious  agent 
and  the  intensity  of  its  action,  the  kind  of  tissue  acted  upon  and 
the  variations  in  the  resistance  of  the  individual.  Certain  condi- 
tions may  be  recognized  as  essential  to  the  process.  There  is 
always  some  change  produced  in  the  tissue  by  the  injurious  agent; 
certain  disturbances  in  the  circulation  take  place  leading  to  an 
exudation  of  fluid  and  cells  from  the  blood  vessels;  there  is  a  new 
formation  of  cells  in  the  part. 

It  may  or  may  not  be  possible  to  demonstrate  the  tissue  lesions 
produced  by  the  injurious  agent  since  there  may  be  injury  to  cells 
without  morphological  change  and  shown  only  by  abnormal  re- 
action.   The  greatest  degree  of  injury  is  shown  by  necrosis.    This 
may  affect  the  cells  alone,  or  there  may  be  combined  with  it  de- 
struction of  the  intercellular  substances  and  coagulation  of  the 
blood  and  of  the  tissue  fluids.     Slight  changes  consisting  in  swelling 
and  vacuolization  of  protoplasm  or  changes  in  nuclear  structures 
may  be  produced.    By  the  effect  of  trauma  the  normal  relations 
of  tissues  may  be  disturbed,  blood  vessels  may  be  ruptured  and 
cells  separated  from  their  relations  with  the  intercellular  substances. 
THE  VASCULAR  PHENOMENA.    The  sequence  of  these  is  best 
observed  by  the  direct  microscopic  examination  of  a  loop  of  the 
exposed  mesentery  of  a  curarized  and  pithed  frog.    The  exposure 
of  this  tissue  to  the  air  produces  a  sufficient  degree  of  injury,  and 
the  greater  the  care  taken  to  avoid  undue  injury  in  making  the 
exposure,  the  better  will  be  the  results.    The  first  change  seen  is  a 
slight  contraction  of  the  arteries  and  a  diminution  in  the  rapidity 
of  the  circulation  in  capillaries  and  veins.    This  is  temporary, 
difficult  to  demonstrate  and  is  followed  quickly  by  dilatation  of 
all  the  vessels  and  a  greatly  accelerated  blood  flow.    The  dilatation 
is  most  marked  in  the  veins,  less  in  the  capillaries  and  least  in  the 
arteries.    The  axial  core  of  red  corpuscles  and  the  plasma  zone  in 
which  the  white  corpuscles  move  remains  as  in  the  normal.    The 

46 


INFLAMMATION  47 

current  in  the  dilated  vessels  becomes  slower  and  the  white  cor- 
puscles move  relatively  more  slowly  than  the  red;  in  consequence 
of  which  they  accumulate  in  the  capillaries  and  veins  lining  the 
walls  of  the  latter.  Single  corpuscles  temporarily  cling  to  the  walls 
and  then  are  carried  further  by  the  current.  Finally,  numbers  of 
white  corpuscles  become  attached  to  the  wall  of  the  vessel;  here 
they  become  amoeboid,  and,  seemingly,  by  amoeboid  activity,  pass 
through  the  walls  of  the  vessels  and  appear  in  the  tissue.  As  the 
stream  becomes  slower  the  plasma  zone  disappears  and  the  cor- 
puscles fill  the  vessel.  The  emigration  of  the  leucocytes  takes  place 
chiefly  in  the  small  veins,  to  a  less  extent  in  the  capillaries,  and, 
under  usual  conditions,  not  at  all  in  the  arteries.  The  red  cor- 
puscles, though  in  much  smaller  numbers,  pass  through  the  walls 
of  the  capillaries;  diapedesis.  They  become  attached  at  one  point 
to  the  capillary  wall  and  stretch  out  in  the  current  like  elastic  bags. 
A  small  protrusion  of  the  corpuscle  appears  opposite  the  point  of 
attachment  and  the  entire  corpuscle  seems  to  pass  through  a  minute 
opening  in  the  wall,  very  much  in  the  same  way  that  partially  filled 
elastic  bags  can  be  passed  through  a  small  opening.  Not  only  do 
the  corpuscles  pass  through  the  vessels,  but  the  blood  fluid  passes 
out  also.  This  cannot  be  seen,  but  both  white  and  red  corpuscles 
which  have  passed  into  the  tissues  are  carried  away  from  the  vessels 
by  moving  currents.  When  fresh  inflamed  tissues  are  quickly 
fixed,  then  sectioned  and  stained,  conditions  representing  every 
stage  of  the  process  as  it  occurs  in  the  mesentery  can  be  observed, 
and  the  emigration  better  studied  than  in  the  living  tissue. 

These  conditions  in  the  inflamed  part  give  rise  to  certain  phe- 
nomena, in  part  objective,  in  part  subjective,  which  are  described 
as  the  cardinal  signs  of  inflammation.  They  are  heat,  redness, 
swelling  and  pain. 

There  is  a  subjective  sense  of  heat  and  if  the  temperature  of  an 
inflamed  area  on  the  surface  be  taken  it  will  be  found  hotter  than 
a  corresponding  normal  part.  There  is  no  formation  of  heat  in 
the  inflamed  part,  and  the  temperature  never  rises  above  that  of 
the  interior  of  the  body.  The  heat  is  due  to  the  more  rapid  cir- 
culation, more  heat  being  brought  to  the  surface  from  the  interior 
by  the  accelerated  arterial  flow. 

Redness  is  due  to  the  presence  of  a  greater  amount  of  blood  in 
the  part.  When  the  circulation  is  active,  the  color  is  a  bright  red; 


48  PATHOLOGY 

when  the  blood  stagnates  in  the  dilated  vessels,  it  loses  its  oxygen 
and  the  color  is  dusky  and  bluish. 

Although  a  certain  amount  of  turgor  or  swelling  is  produced  by 
the  dilatation  of  the  vessels,  this  is  a  negligible  factor  as  compared 
with  the  effect  of  the  exudation.  The  total  amount  of  exudation 
cannot  be  determined  by  the  degree  of  swelling,  there  is  an  increased 
outflow  through  the  lymphatics  and  the  swelling  represents  merely 
the  exudation  which  remains.  The  fluid  distends  the  tissue  spaces 
and  separates  the  connective  tissue  fibres.  It  passes  readily  to 
surfaces,  as  in  the  lung,  and  may  collect  in  serous  cavities.  In 
inflammation  of  the  skin  the  exudate  formed  in  the  corium  passes 
through  the  lower  layers  of  the  epidermis  and  elevates  the  im- 
penetrable horny  layer,  forming  blisters.  In  the  inflamed  mucous 
membrane  it  passes  through  the  more  loosely  connected  epithelial 
cells  to  the  surface,  so  that  swelling  may  not  be  a  prominent  feature. 
By  means  of  the  exudation,  red  corpuscles  may  be  carried  to  sur- 
faces and  into  the  tissue  spaces.  The  chemical  examination  of  the 
exudate  has  shown  that  it  is  richer  in  protein  than  the  lymph,  but 
the  salt  content  is  the  same.  Usually  fibrin,  to  a  greater  or  less 
extent,  is  formed  in  the  exudation.  Fibrinogen  is  present  in  the 
exudate  and  fibrin  ferment  is  provided  by  the  disintegration  of 
leucocytes  and  tissue  cells.  Necrotic  cells  in  the  tissue  may  form 
nodal  points  about  which  the  fibrin  collects.  A  large  amount  of 
fibrin  in  the  exudate  gives  a  greater  degree  of  induration  to  the 
swelling  and  indicates  a  more  severe  type  of  inflammation.  When 
the  conditions  for  the  production  of  fibrin  are  present  in  the  epithe- 
lium of  a  mucous  membrane,  the  exudate  coming  from  below 
coagulates  on  the  surface  forming  a  membrane.  The  exudate  may 
extend  far  beyond  the  site  of  injury  and  be  found  in  normal  tissues. 
The  cells  of  the  exudate  form  one  of  its  most  characteristic  features. 
All  the  cells  of  the  blood  enter  into  it  to  a  varying  degree.  The 
polynuclear  leucocytes  play  the  most  important  part  and  in  certain 
inflammations,  especially  those  produced  by  the  pyogenic  bacteria, 
may  be  the  only  cells  which  emigrate.  When  the  different  leu- 
cocytes take  part  in  the  exudation,  the  polynuclears  are  always  the 
first  to  appear.  Eosinophile  cells  are  most  numerous  in  the  in- 
flammations produced  by  animal  parasites,  but  a  few  usually  are 
present  in  any  exudation.  The  mononucle'ar  cells  emigrate  later 
than  the  polynuclears  and  rarely  are  present  in  large  numbers. 


INFLAMMATION  49 

Lymphocytes  often  are  found  in  very  large  numbers,  particularly 
in  cases  where  the  cause  persists  and  the  inflammation  lasts  for 
days.  The  numbers  in  the  blood  never  seem  sufficient  to  furnish 
the  numbers  in  the  tissue  by  emigration.  In  hardened  sections 
they  may  be  seen  in  mural  arrangement  within  the  vessels  and  in 
various  stages  of  emigration.  Blood  platelets  never  are  found  in 
the  exudation.  They  seem  not  to  have  the  amoeboid  power  which 
would  allow  of  active  emigration,  nor  the  degree  of  solidity  neces- 
sary for  passive  transmission. 

The  tissue  changes  will  be  described  more  fully  under  degener- 
ation and  repair. 

Inflammations  are  divided  into  acute  and  chronic,  but  there  is  no 
sharp  separation,  the  length  of  time  the  inflammation  has  lasted 
and  the  conditions  produced  serving  as  criteria.  The  best  examples 
of  acute  inflammations  are  given  in  those  injuries  of  tissue,  which 
are  produced  by  a  cause  acting  temporarily,  as,  for  example,  minor 
degrees  of  heat.  In  the  chronic  inflammations  the  cause  persists 
and  the  inflammation  lasts  during  the  continuance  of  the  cause, 
or  until  the  tissues  have  adapted  themselves  to  the  new  environ- 
ment produced.  The  frequent  repetition  of  inflammation  in  a  part 
may  lead  to  chronic  inflammation;  the  repair  of  the  tissue  after 
each  successive  injury  is  progressively  less  perfect  and  finally  a 
condition  of  increased  vulnerability  is  produced,  in  which  causes, 
to  which  the  normal  tissues  would  adapt  themselves,  produce 
injury  and  inflammation. 

Various  divisions  of  inflammation  are  made  depending  upon  the 
character  of  the  exudate.  Serous  inflammation  is  produced  by  a 
mild  degree  of  injury,  and  the  exudate  is  almost  entirely  fluid.  The 
exudate  which  is  formed  by  sunburn,  or  by  the  action  of  mild 
caustics,  is  of  this  character.  The  fluid  which  collects  in  the 
blisters  contains  very  few  leucocytes  and  clots  feebly.  In  fibrinous 
inflammations  the  exudate  contains  a  large  amount  of  fibrin.  The 
amount  of  fibrin  seems  to  be  influenced  by  situation,  being  most 
abundant  where  the  exudate  passes  to  a  surface.  It  also  is  in- 
fluenced by  the  cause,  thus  inflammation  produced  by  certain 
bacteria  usually  takes  on  a  fibrinous  character.  Such  an  exudate 
combined  with  necrotic  epithelial  cells  forming  a  membrane  on  a 
mucous  surface  is  called  diphtheritic.  Such  conditions  most 
frequently  are  produced  in  the  mucous  membrane  of  the  throat  by 


50  PATHOLOGY 

the  action  of  the  diphtheria  bacillus  but  may  be  produced  by  other 
organisms  and  in  other  situations.  Hemorrhagic  inflammation  is 
characterized  by  the  presence  of  large  numbers  of  red  blood  cor- 
puscles in  the  exudate.  It  indicates  a  severe  type  of  inflammation 
and  the  condition  of  the  individual  exerts  a  more  important  in- 
fluence than  in  the  formation  of  other  exudations.  In  badly 
nourished  individuals,  especially  in  the  cachexia  of  cancer,  in  certain 
diseases  affecting  the  character  of  the  blood  or  blood  vessels,  it  is 
more  likely  to  occur.  The  special  characteristics  of  the  purulent 
exudation  and  abscess  will  be  considered  with  the  pyogenic  bacteria. 
Catarrhal  inflammation  is  an  indefinite  term  and  indicates  the 
increased  discharge  from  an  inflamed  mucous  surface.  The  fluid 
discharged  is  in  great  part  the  exudation  of  both  fluid  and  cells 
which  passes  through  the  comparatively  loosely  connected  epithe- 
lial cells.  This  is  added  to  by  an  increased  secretion  from  the 
mucous  glands. 

The  pain  of  an  inflamed  part  is  attributed  usually  to  the  pressure 
exerted  by  the  exudate  upon  the  sensory  nerves.  Parts,  such  as  the 
peritoneum,  which  ordinarily  have  but  little  sensation  become 
exquisitely  painful  when  inflamed.  In  general,  the  pain  is  greater 
when  the  exudation  takes  place  in  dense  unyielding  tissues  as  the 
periosteum.  There  usually  is  greater  pain  in  inflammation  of  the 
corium  than  in  the  loose  subcutaneous  connective  tissue.  Certain 
bacterial  inflammations  produce  more  pain  than  the  same  condition 
due  to  another  cause.  A  rapidly  forming  exudation  in  the  corium 
in  urticaria  is  not  painful.  Although  the  tissue  pressure  exerts 
some  influence,  and  in  certain  cases,  a  great  influence,  it  is  not  the 
sole  factor  in  causing  pain.  In  addition,  there  is  the  direct  action 
of  the  injurious  cause  on  the  sensory  nerves,  possibly  added  to  by 
the  action  of  toxic  substances  formed  in  the  inflamed  part. 

There  is  no  adequate  explanation  for  the  changes  seen  in  inflam- 
mation. They  occur,  the  conditions  for  their  occurence  are  known 
and  they  can  all  be  produced  experimentally;  but  the  exact  nature 
of  the  primary  change  produced  by  the  injury  is  not  known  nor  in 
what  way  the  changes  act  in  bringing  about  the  vascular  phenomena. 
Various  hypotheses  have  been  advanced  in  explanation.  The 
dilation  is  generally  attributed  to  a  change  in  the  vessel  produced 
either  directly  by  the  injurious  agent  or  by  the  toxic  substances 
tVip  injured  tissues,  these  acting  either  hy 


INFLAMMATION  51 

of  the  vasodilators  or  by  paralysis  of  the  vaso-constrictors  or  by 
direct  paralysis  of  the  muscle  fibres.  The  dilatation  is  seen,  how- 
ever, in  the  vessels  at  a  distance  from  the  injured  area.  The  fluid 
exudation  is  attributed  to  the  same  cause,  a  change  in  the  walls 
of  the  vessels  whereby  they  become  more  permeable.  It  has  been 
supposed  also  that  the  osmotic  relations  between  blood  and  tissue 
fluids  is  altered,  the  osmotic  pressure  in  the  latter  being  raised  by 
the  formation  of  crystalloid  substances  from  the  molecular  destruc- 
tion of  cells  and  tissue.  The  passage  of  the  leucocytes  through  the 
walls  usually  is  attributed  to  their  amoeboid  activity,  and  the 
appearances  are  indicative  of  this,  whether  the  process  is  directly 
observed  or  the  stages  studied  in  sections  of  hardened  tissues.  On 
the  other  hand,  it  is  held  that  their  passage  is  due  to  filtration,  they 
being  forced  through  by  increased  intravascular  pressure.  In 
favor  of  this  is  the  fact  that  the  non-amceboid  red  corpuscles  pass 
through  and  also  it  can  be  shown  experimentally  that  fat  globules 
pass  through  in  such  conditions.  When  the  vessels  in  an  inflamed 
area  are  injected  with  silver  nitrate  solution,  thus  demonstrating 
the  endothelial  lines  of  junction,  the  emigration  is  seen  to  take  place 
chiefly  at  such  lines  of  junction.  Whether  or  not  there  are  actual 
openings,  stomata,  at  these  points  through  which  the  corpuscles 
pass,  is  uncertain.  In  regard  to  the  formation  of  the  exudation, 
it  must  be  remembered  that  the  capillary  wall  is  a  very  thin  mem- 
brane, probably  colloidal  in  character,  in  the  dilated  condition 
much  thinner  than  normal,  and  this  physical  change  favors  both 
filtration  and  osmosis.  The  slowing  of  the  current  in  the  dilated 
vessels  may  be  attributed  in  part,  at  least,  to  increased  friction  of 
the  blood;  this  being  produced  by  the  diminution  of  fluid  owing  to 
the  exudation,  by  the  opposition  given  by  the  adherent  corpuscles 
and  the  hypothetical  change  in  the  walls. 

The  leucocytes  hi  the  exudation  collect  around  areas  of  necrotic 
tissue  and  in  bacterial  inflammations  around  bacteria.  When  the 
centre  of  the  cornea  is  injured  the  leucocytes  enter  the  cornea  at  the 
periphery  and  pass  to  the  injured  area  by  means  of  the  communicat- 
ing corneal  spaces  and  between  the  fibres.  This  indicates  that 
some  means  of  communication  must  exist  between  the  injured  area 
and  the  leucocytes,  and  there  can  be  no  other  means  of  communica- 
tion than  by  the  action  of  chemical  substances.  This  influence 
which  chemical  substances  exert  on  the  motion  of  living  organisms 


52  PATHOLOGY 

is  known  as  chemotaxis  or  chemotropism.  Certain  substances  are 
known  to  attract,  others  to  repel,  these  phenomena  being  known, 
respectively,  as  positive  and  negative  chemotaxis.  The  effect  in 
causing  motion  in  a  certain  direction  is  attributed  to  a  stimulation 
of  the  leucocyte  on  the  side  toward  the  source  of  the  stimulus,  thus 
directing  motion.  The  action  of  chemotactic  substances  affects 
not  only  the  leucocytes  in  the  tissues,  but  also  those  in  the  circulat- 
ing blood.  In  the  vessels  outside  the  inflamed  cornea  the  mural 
accumulation  of  leucocytes  takes  place  chiefly  on  the  side  of  the 
vessel  towards  the  cornea.  The  emigration  of  leucocytes  does  not 
take  place  blindly,  for  in  different  conditions  only  certain  leucocytes 
emigrate.  In  the  copious  sero-fibrinous  exudation  produced  in  the 
scrotum  of  a  rabbit  by  freezing,  mononuclear  cells  are  found,  and 
in  most  bacterial  inflammation  only  the  polynuclear  cells  emigrate. 

If  the  peritoneum  of  an  animal  be  inflamed  by  the  injection  of 
hot  water  and  the  blood  be  examined  after  the  exudation  has  begun, 
the  leucocytes  will  be  found  to  be  reduced  in  number  depending 
upon  the  rapidity  of  emigration.  This  condition  is  called  hypoleu- 
cocytosis.  The  number  of  leucocytes  then  slowly  increases  until 
they  exceed  the  normal.  Such  an  increase  is  known  as  hyperleu- 
cocytosis  and  in  extensive  acute  inflammations  in  man,  as  in  crou- 
pous  pneumonia,  there  may  be  60,000  instead  of  8000  per  cm. 
The  examination  of  the  bone  marrow  shows  that  in  the  beginning 
the  leucocytes  diminish  in  number  due  to  their  rapid  passage  into 
the  blood.  There  then  takes  place  a  rapid  new  formation  of  leu- 
cocytes. The  marrow  changes  its  character,  becoming  red,  there 
are  abundant  nuclear  figures  in  the  cells  and  the  newly  formed 
leucocytes  pass  into  the  vessels.  Changes  also  are  seen  in  the 
lymph  nodes  which  receive  the  lymphatics  from  an  inflamed  area. 
They  usually  are  swollen  and  redder  than  normal.  On  micro- 
scopic examination  the  lymph  sinuses  are  found  dilated  and  contain 
numerous  cells,  some  of  which  represent  the  exudation  cells  which 
are  brought  to  the  nodes  by  the  lymph  stream,  and  some  are  newly 
formed.  The  lymph  brings  to  the  node  injurious  substances  of 
various  sorts  which  may  produce  necrosis  or  may  stimulate  the 
node  to  the  formation  of  new  cells. 

HEALING  AND  REPAIR.  The  changes  which  have  been  described 
will  continue  in  progress  until  the  injurious  agent  is  removed  or  the 
tissues  have  adapted  themselves  to  its  presence.  The  fluid  exuda- 


INFLAMMATION  53 

tion  plays  an  important  part  in  the  dilution  and  removal  of  injurious 
chemical  substances.  In  inflammation  produced  by  bacteria  it 
constantly  brings  to  the  part  bactericidal  or  immune  substances. 
The  presence  of  the  exudation  in  the  tissues  constitutes  an  abnormal 
condition  and  in  the  process  of  healing  it  is  removed.  The  fluid 
exudation  is  removed  from  the  tissues  by  the  lymphatics  and  to  a 
less  extent  by  the  blood  vessels.  Leucocytes  and  red  corpuscles 
pass  into  the  lymphatics  and  may  be  found  in  the  sinuses  of  the 
adjacent  lymph  nodes.  Many  cells  both  white  and  red  undoubtedly 
disintegrate  in  the  tissues  or  are  destroyed  by  phagocytic  cells. 
When  many  red  corpuscles  are  in  the  exudation,  blood  pigment  as 
an  indication  of  their  destruction  remains  in  the  tissue.  Fibrin 
cannot  be  absorbed,  and  is,  in  part,  liquefied  by  a  process  akin  to 
digestion.  This  is  termed  autolysis  and  is  best  seen  in  the  lique- 
faction of  the  fibrinous  exudation  in  pneumonia.  The  process  is 
due  to  a  ferment  action,  the  ferment  being  provided  by  the  poly- 
nuclear  leucocytes.  All  cells,  probably,  contain  such  autolytic 
enzymes  which  in  the  living  cells  are  held  in  check  and  become 
operative  after  the  death  of  the  cell.  The  liquefaction  and  removal 
of  fibrin  does  not  take  place  readily  when  the  exudation  is  on  a 
serous  surface.  It  is  then  removed  by  the  process  of  organization. 
In  this  a  cellular  vascular  tissue  grows  from  the  adjacent  living 
tissue  and  substitutes  itself  for  the  exudation  which  disappears  as 
the  growth  advances.  Such  a  tissue  is  termed  granulation  tissue 
and  its  formation  is  best  studied  in  the  ulcer.  This  is  a  loss  of 
substance  on  a  surface  involving  both  the  surface  covering,  and,  to 
some  extent,  the  underlying  tissue.  In  the  process  of  healing  an 
exudation  consisting  of  red  and  white  cells  and  fibrin  is  formed, 
filling  the  loss  and  into  this  the  granulation  tissue  grows  as  in 
organization.  New  blood  vessels  form  from  the  underlying  small 
veins  and  capillaries  by  the  proliferation  of  the  endothelial  cells. 
The  endothelial  cells  enlarge,  the  nuclei  become  more  prominent, 
and  they  send  out  large  pointed  processes  which  become  nucleated 
by  nuclear  division  in  the  parent  cell.  Cell  division  and  growth 
go  on  rapidly  until  a  small  mass  of  cells  is  formed,  which  grow  into 
the  exudation.  The  elongated  cells  become  laterally  disposed, 
communication  with  the  old  vessels  is  established  and  new  vessels 
thus  are  formed.  The  new  growing  vessel  always  has  numerous 
pointed  protoplasmic  processes  at  its  apex.  These  unite  with 


54  PATHOLOGY 

similar  processes  from  adjacent  vessels,  the  vascular  formation 
proceeds  along  the  communication  and  in  this  way  loops  are  formed 
making  a  circulation  possible.  The  name  "granulation  tissue  "  is 
derived  from  the  granular  appearance  of  the  surface  of  the  ulcer, 
as  seen  by  the  naked  eye,  the  granules  corresponding  to  small 
masses  of  newly  formed  vessels.  The  new  vessels  are  characterized 
by  the  large  size  of  the  endothelial  cells,  in  which  nuclear  figures 
are  common,  and  by  a  constant  emigration  of  leucocytes  from  them. 
The  formation  of  new  connective  tissue  cells  proceeds  along  with 
the  new  formation  of  blood  vessels,  sometimes  in  contact  with  them, 
sometimes  between  them,  and  intercellular  fibrils  appear  in  relation 
with  the  cells.  As  this  tissue  penetrates  the  fibrin  the  latter  dis- 
appears often  first  becoming  hyalin,  and  the  leucocytes  in  part 
disintegrate  as  is  shown  by  the  nuclear  detritus,  and  in  part  they 
are  destroyed  by  phagocytic  cells. 

PHAGOCYTOSIS.*  Cells,  bacteria  and  other  insoluble  substances 
may  be  removed  by  phagocytosis  which  essentially  is  an  intra- 
cellular  digestion.  Certain  cells  like  amoebae  take  into  their  cyto- 
plasm substances  which  come  in  contact  with  them,  there  being, 
however,  in  the  different  cells  a  choice  as  to  the  substances  taken 
up.  The  invasion  of  necrotic  cells  and  tissues  by  polynuclear 
leucocytes  is  not  identical  with  phagocytosis.  The  leucocytes 
under  such  conditions  disintegrate  and  probably  assist  in  the  autol- 
ysis  by  the  liberation  of  enzymes.  Nor  can  the  presence  of  bacteria 
within  cells  always  be  taken  as  an  indication  that  they  are  being 
destroyed  by  phagocytosis,  since  certain  bacteria  seem  to  find  the 
optimum  conditions  for  existence  in  intracellular  life.  The  poly- 
nuclear  leucocytes  are  generally  phagocytic  for  bacteria,  the  mono- 
nuclear  endothelial  cells  of  the  blood  to  a  much  less  extent  and  the 
cells  of  the  tissue  probably  to  a  very  slight  extent.  Neither  cells 
nor  other  substances  than  bacteria  are  taken  up  by  the  poly- 
nuclear  leucocytes.  The  most  generally  active  phagocytic  cells  are 
those  produced  by  proliferation  of  tissue  cells.  All  types  of  endo- 
thelial cells,  those  in  the  blood,  the  new  cells  derived  from  prolifera- 
tion of  endothelium  of  blood  or  lymphatic  vessels,  or  the  wandering 
endothelial  cells  of  the  tissue  are  phagocytic  in  high  degree  and 
chiefly  for  other  cells  and  for  various  foreign  bodies.  Proliferating 
connective  tissue  cells  are  also  phagocytic,  but  to  a  less  degree. 

*  Phagocytosis  in  its  immunological  relations  will  be  discussed  under  infections. 


INFLAMMATION  55 

The  cells  derived  from  proliferation  of  the  lining  cells  of  serous 
cavities  form  a  great  part  of  the  phagocytic  cells  of  the  body,  and 
the  same  is  true  of  the  closely  kindred  cells  lining  the  lung  alveoli. 
The  more  highly  differentiated  cells  of  the  body  do  not  become 
phagocytic  except  under  certain  conditions.  All  those  tissue  cells 
whose  phagocytic  powers  are  directed  chiefly  towards  other  cells, 
form  the  macrophages  of  Metschnikoff,  the  polynuclear  cells  are 
the  microphages.  Cells  belonging  to  the  lymphoid  series  are  never 
phagocytic  and,  on  the  other  hand,  no  cells,  with  the  possible  excep- 
tion of  the  red  blood  corpuscles,  are  so  generally  the  object  of  phag- 
ocytosis. Cellular  digestion  is  carried  on  not  only  directly  within 
the  cytoplasm,  but  in  contact  with  it.  Phagocytic  cells  may  join 
together  forming  a  syncitial  mass,  or  giant  cell,  which  may  enclose 
a  foreign  body  or  form  an  extensive  surface  contact  with  it.  Most 
of  the  giant  cells  found  in  pathological  tissues  are  formed  in  this 
way.  Phagocytosis  plays  an  important  part  in  the  infectious 
diseases  and  in  the  most  varied  pathological  processes.  In  phag- 
ocytosis the  family  relationship  is  respected,  cells  of  the  same  type 
not  devouring  one  another;  the  red  corpuscles  and  lymphoid  cells 
are  the  strangers  to  whom  hospitality  usually  is  extended. 

REPAIR.  The  removal  of  the  exudate  is  but  one  of  the  steps  in 
repair.  Any  injury  or  destruction  of  tissue  must  be  made  good  by 
the  activity  of  the  tissue  cells.  The  leucocytes  of  the  exudation 
take  no  part  in  tissue  regeneration.  In  the  tissues  there  are  cells 
intimately  associated  with  this,  as  the  endothelium  of  blood  and 
lymph  vessels,  the  connective  tissue  cells,  the  nerves  and  differen- 
tiated epithelial  structures,  and  cells  which  are  present  in  variable 
numbers  and  do  not  form  an  essential  part  of  the  tissue,  as  the 
wandering  polynuclear  leucocytes  and  endothelial  cells  and  the 
various  lymphoid  cells.  The  tissue  polynuclear  cells  need  not  be 
considered;  whatever  their  function  is,  they  take  no  more  part  in 
repair  than  do  the  polynuclear  cells  in  the  exudate.  Injury  or 
destruction  of  simple  covering  epithelium  is  made  good  quickly  by 
new  formation  of  epithelium  or  by  the  recovery  of  cells  slightly 
injured.  How  great  a  degree  of  injury  cells  can  sustain  and  recover 
is  uncertain.  The  epithelium  lining  serous  cavities  and  the  lining 
epithelium  of  the  lung  alveoli  has  great  power  of  proliferation, 
quickly  covers  over  defects  and  produces  free  phagocytic  cells.  In 
certain  cases  there  is  marked  proliferation  of  the  endothelial  cells. 


56  PATHOLOGY 

These  may  form  a  thick  cellular  lining  in  the  larger  vessels,  emigrate 
and  contribute  to  the  phagocytic  cells  of  the  tissue.  In  vessels  of 
capillary  character  large  numbers  of  endothelial  cells  are  formed 
and  these  in  the  vicinity  of  the  vessels  may  appear  as  branched 
cells  not  unlike  fibroblasts.  The  function  of  these  endothelial  cells, 
apart  from  the  part  they  play  in  phagocytosis,  is  unknown.  It 
cannot  be  shown  that  they  form  intercellular  substances.  There 
is  a  great  departure  in  the  size  and  form  of  such  endothelial  cells 
from  those  represented  in  the  endothelial  cells  of  the  blood,  but  the 
transitional  stages  can  be  seen.  The  lymphocytes  in  the  healing 
tissue  appear  as  small  lymphocytes  and  as  plasma  cells.  In  certain 
forms  of  chronic  inflammation,  both  simple  and  infectious,  plasma 
cells  may  be  present  in  enormous  numbers  very  frequently  as  masses 
around  the  vessels.  They  usually  are  oval,  the  long  diameter 
7~Q/z,  the  short  5-7^,  but  the  size  and  shape  varies.  The  outline 
usually  is  smooth,  but  blunt  processes  indicative  of  amoeboid 
movement  are  often  seen.  The  cytoplasm  is  dense,  without 
evident  granulation  and  stains  strongly  with  basic  dyes.  The 
nucleus  is  round  and  is  eccentrically  placed  in  the  cell.  It  has  the 
characteristics  of  the  lymphocyte  nucleus,  but  stains  more  deeply 
and  has  more  and  larger  clumps  of  chroma  tin.  In  the  larger  cells 
two  or  more  nuclei  often  are  seen.  The  cells  are  capable  of  pro- 
liferation and  nuclear  figures  are  found  in  them.  The  source  of 
these  cells  is  uncertain.  Transitions  between  them  and  the  small 
lymphocytes  can  be  seen  and  they  appear,  in  part  at  least,  to 
develop  from  these.  The  part  they  play  in  the  process  of  tissue 
repair  is  not  known. 

Repair  of  the  connective  tissue  takes  place  by  a  new  formation  of 
connective  tissue  cells  and  intercellular  substance.  The  connective 
tissue  cells  become  swollen,  basophilic,  stellate  in  shape,  or  have 
long,  widely  extended,  branching  processes.  The  nucleus  swells, 
usually  is  oval  in  shape  and  the  chromatin  is  increased.  Nuclear 
figures  may  be  seen  in  these  cells  as  early  as  eighteen  hours  after  the 
injury.  In  the  injured  cornea  the  extension  of  the  new  cells  into 
the  area  of  injury  takes  place  much  in  the  same  way  that  new  blood 
vessels  are  formed.  A  long  process  is  given  off  from  a  cell  and  the 
nuclei  resulting  from  the  division  of  the  parent  nucleus  move  up 
into  the  process  and  the  cytoplasm  increases  around  each  new  nu- 
cleus, forming  new  branched  cells.  In  the  organizing  exudate  the 


INFLAMMATION  57 

new  cells  seem  to  move  along  such  supporting  tissue  as  the  newly 
formed  blood  vessels.  It  is  not  uncommon  to  find  cell  fragments 
which  retain  the  characteristics  of  the  cytoplasm  given  off  from  both 
polynuclear  and  plasma  cells,  and  such  fragments,  and  even  entire 
cells,  are  taken  up  in  the  growing  fibroblasts.  It  is  not  possible  to 
arrive  at  any  conclusion  as  to  the  manner  in  which  the  intercellular 
substances  are  formed  from  the  cells.  The  fibres  appear  between 
the  cells  and  cell  processes  seem  to  pass  into  fibrils.  Two  sorts 
of  fibrils  appear,  the  ordinary  small  fibrils  of  the  white  fibrous  tissue 
and  large  fibrils  which  have  the  same  relation  to  the  cells  as  the 
fibrils  of  smooth  muscle.  This  process  is  almost  invariably  ac- 
companied by  a  new  formation  of  vessels,  which  takes  place  as 
described  in  organization.  The  extent  of  the  connective  tissue 
formation  and  its  character  depends  upon  the  degree  of  injury.  In 
a  simple,  clean,  incised  wound  of  the  skin  which  is  brought  closely 
together,  a  very  small  amount  of  exudation  containing  little  fibrin 
and  few  leucocytes  is  formed  between  the  opposing  surfaces.  The 
adjoining  connective  tissue  cells  proliferate  to  a  slight  extent  and 
give  rise  to  a  minimum  amount  of  intercellular  substance  which 
forms  the  permanent  union.  In  the  case  of  large  loss  of  substance, 
as  in  an  ulcer  or  in  chronic  inflammation  about  a  persistent  cause, 
such  as  a  foreign  body,  the  new  formation  may  be  much  greater  and 
differs  in  character  from  that  formed  in  the  simple  incision.  The 
coarse  fibrils  are  formed  to  a  much  greater  extent,  and  all  the  fibrils 
seem  to  fuse  together,  forming  dense  masses;  the  newly  formed 
blood  vessels  in  great  part  disappear  leaving  the  tissue  anaemic; 
most  of  the  cells  also  disappear,  leaving  the  tissue  less  cellular  than 
normal.  There  results  a  hard  white  tissue,  the  cicatricial  tissue  or 
scar,  which,  both  to  the  naked  eye  and  microscopically,  is  sharply 
differentiated,  and  which  has  a  marked  tendency  continually  to 
contract. 

SUMMARY.  An  injury  to  tissue  is  followed  by  increased  afflux  of 
blood  and  by  exudation.  In  the  process  of  recovery  the  fluid 
exudate  is  removed  by  lymphatic  and  blood  absorption.  The  cells 
of  the  exudate  in  part  pass  into  lymphatics  and  are  removed,  in 
part  undergo  autolysis  or  are  taken  up  by  phagocytic  cells,  or  they 
may  collect  into  dense  masses  which  after  necrosis  become  calcified 
or  they  may  undergo  organization.  Cysts  may  be  formed  by  ab- 
sorption and  partial  organization  of  the  necrotic  tissue  and  exudate. 


58  PATHOLOGY 

Fibrin  in  the  exudatc  may  be  dissolved  by  the  action  of  enzymes 
given  of!  by  the  leucocytes,  or  newly  formed  connective  tissue  may 
grow  into  and  replace  it.  The  processes  of  repair  take  place  from 
the  tissue  cells,  the  cells  of  the  exudate  taking  no  part  in  it.  Repair 
of  the  injury  is  rarely  perfect;  in  the  place  of  the  injured  tissue  scar 
tissue  is  substituted,  which  is  more  vulnerable  to  subsequent  injury 
and  less  perfect  in  function. 

EXPERIMENTS.  The  experiments  possible  on  the  subject  of  in- 
flammation are  so  numerous  and  varied  that  only  a  relatively 
small  group  can  be  performed.  Most  important  seem  to  be  those 
connected  with  the  processes  of  exudation,  phagocytosis  and  repair. 
In  the  first  group  are  included  the  study  of  the  rabbit's  ear  after 
exposure  to  water  at  53°  C.  for  three  minutes.  Both  this  and  a 
similar  study  of  the  rabbit's  ear  rubbed  with  croton  oil  give  the 
cardinal  symptoms  of  inflammation.  The  same  experiments  should 
be  performed  on  rabbits  whose  cervical  sympathetic  has  been 
divided  in  the  neck. 

The  production  of  leucocytic  exudate  in  the  rabbit's  pleura  by 
the  injection  of  a  few  cubic  centimeters  aleuronat  suspension,  of  a 
purulent  exudate  by  the  injection  of  i  c.c.  bouillon  culture  bacillus 
coli  communis  or  staphylococcus  pyogenes  aureus,  and  the  produc- 
tion of  a  sero-fibrinous  exudate  by  means  of  the  injection  into  the 
pleura  of  2  c.c.  turpentine,  gives  opportunity  for  the  study  of 
exudates  and  of  the  different  etiological  relations  of  the  exudate. 
The  localized  abscess  can  be  produced  by  the  subcutaneous  injec- 
tion of  a  fresh  culture  of  staphylococcus  aureus  or  colon  bacillus, 
arid  the  metastatic  abscesses  of  kidney  and  heart  produced  by  in- 
jection of  i  c.c.  twenty-four-hour  bouillon  culture  of  staphylococcus 
aureus  into  the  posterior  auricular  vein  of  the  rabbit.  Both  these 
experiments  should  include  careful  microscopical  examination  of 
the  pus  and  of  the  diseased  tissues. 

For  the  study  of  phagocytosis  reference  to  the  experiment  in 
pigmentation  (see  page  45)  is  important  for  the  demonstration  of 
phagocytosis  of  mineral  inert  particles.  For  the  study  of  phago- 
cytosis of  animal  cells  3  c.c.  of  a  mixture  of  equal  parts  salt  solution 
and  defibrinated  pigeon's  blood  should  be  injected  into  the  peri- 
toneal cavity  of  a  guinea  pig.  Intracellular  inclusion,  vacuole 
formation  and  digestion  can  be  studied  by  withdrawing  some  of  the 
material  in  the  peritoneum  by  means  of  a  drawn  out  capillary 


INFLAMMATION  59 

pipette  at  the  end  of  one,  two  and  three  days,  making  spreads  and 
staining  with  Wright's  stain.  A  similar  experiment,  using  a  bouil- 
lon culture  of  colon  bacillus  and  withdrawing  the  exudate  at  six, 
twelve  and  twenty-four  hours  shows  the  phagocytosis  of  bacteria. 
Most  important  is  the  influence  of  opsonins  on  phagocytosis.  This 
is  well  illustrated  by  following  these  brief  directions:  Into  a  7  by 
75  mm.  test  tube  two- thirds  filled  with  i  per  cent  sodium  citrate 
solution  drop  twenty  drops  human  blood  (fellow  student),  centri- 
fuge and  collect  the  leucocytes  in  a  warm  drawn  out  glass  pipette. 
Collect  a  small  amount  of  blood  in  a  Wright  tube,  allow  to  clot, 
centrifuge  and  collect  serum.  Make  a  salt  solution  suspension 
(5  c.c.)  of  a  twenty-four-hour  slant  agar  culture  of  staphylococcus 
pyogenes  aureus.  Draw  out  several  glass  pipettes  of  approxi- 
mately uniform  diameter  and  make  a  point  with  a  blue  pencil. 
Fill  to  mark  with  leucocyte  suspension,  permit  some  air  to  run  in, 
then  to  mark  with  bacterial  suspension,  then  more  air,  then  to 
mark  with  salt  solution.  Expel  into  a  sterile  Petri  dish,  mix  and 
allow  to  run  into  pipette  again.  Repeat,  using  a  fresh  tube  and 
serum  instead  of  salt  solution.  Incubate  the  tubes  twenty  minutes, 
make  spreads,  stain  with  Wright's  stain  and  note  the  difference 
produced  by  the  opsonins  in  the  serum. 

For  the  study  of  repair  three  experiments  may  be  chosen. 
After  removing  the  hair  from  two  areas  in  the  opposite  flanks  of  a 
guinea  pig,  the  areas  should  be  washed,  the  animal  anaesthetized 
and  a  linear  wound  made  in  each  area.  Into  one  an  agar  culture 
colon  bacillus  should  be  rubbed,  the  other  to  be  kept  clean.  The 
delay  of  repair  in  the  infected  area  usually  is  striking.  Repair  in 
a  more  complicated  structure  can  be  observed  by  fracturing  the 
livers  of  six  guinea  pigs,  under  complete  ether  anaesthesia,  then 
killing  one  on  alternate  days  and  studying  in  sections  the  sequence 
of  changes.  Repair  in  a  nonvascular  structure  can  be  studied  by 
making,  under  deep  ether  anaesthesia,  a  linear  wound  in  the  cornea 
of  a  rabbit.  The  repair  is  rapid  and  instructive  pictures  can  be 
obtained  by  making  sections  of  the  cornea  at  the  end  of  two  days. 


59  a 


59 


59  c 


59  d 


59  e 


59  f 


59  g 


59  h 


59  J 


59  k 


59m 


59  n 


590 


59  P 


THE  PATHOLOGY  OF  THE  BLOOD. 

In  a  consideration  of  the  pathology  of  the  blood  and  circulation 
certain  normal  conditions  must  be  borne  in  mind.  The  blood  differs 
from  the  other  tissues  of  the  body  in  having  a  fluid  intercellular 
substance  and  in  the  persistence  of  embryonic  processes  of  cell 
formation.  The  blood  has  great  power  of  cell  regeneration,  and  cell 
equilibrium  although  easily  disturbed,  is  rapidly  re-established. 
The  intercellular  fluid  is  complex  in  its  composition,  for  the  blood 
is  the  general  carrier  and  intermediary  agent  for  all  the  tissues. 
The  circulation  of  the  blood  is  maintained  by  the  pumping  action 
of  the  heart  and  the  contractility  of  the  arteries.  The  sectional 
area  of  the  blood  vessels  gradually  increases  from  the  aorta  to  the 
capillaries  reaching  in  the  latter  an  area  800  times  greater  than  that 
of  the  aorta  and  from  this  decreases  again  towards  the  heart.  The 
blood  pressure  diminishes  from  the  aorta  to  the  venae  cavae;  the 
general  estimate  of  pressure  being  no  mm.  of  mercury  in  the 
radial  artery,  20  mm.  of  mercury  in  the  capillaries,  zero  and  in- 
diastole  negative,  at  the  entrance  of  the  venae  cavae  into  the  heart. 
The  blood  supply  of  an  individual  organ  depends  upon  the  blood 
pressure,  the  calibre  of  the  supplying  artery,  the  latter  being  regu- 
lated by  the  action  of  the  vasomotor  nerves  on  the  muscle  cells 
of  the  media  and  the  venous  outflow.  Not  only  has  the  blood 
great  regenerative  capacity,  but  throughout  the  circulation  there 
is  a  remarkable  power  of  adaptability  to  pathological  conditions. 
This  is  effected  by  changes  in  the  blood  itself,  by  changes  in 
the  contractile  force  of  the  heart,  by  changes  in  the  calibre  of  the 
arteries  and  by  changes  in  the  reciprocal  relations  between  the 
blood  and  the  tissue  fluids.  The  blood  pressure  is  the  main  factor 
in  the  production  and  maintenance  of  the  tissue  pressure,  which 
in  turn  results  from  the  interrelation  of  capillary  pressure  and  the 
elasticity  of  the  skin  and  other  tissues. 

Anamia,  although  meaning  literally  absence  of  blood,  is  used  to 
express  a  diminution  in  blood  quantity  (oligamia),  and  a  diminution 
in  the  number  of  corpuscles  (oligocythamia).  The  general  estimate 

60 


THE  PATHOLOGY  OF  THE  BLOOD          61 

of  the  amount  of  blood  in  the  body  varies  from  5  to  7  per  cent  of 
the  body  weight,  and  loss  of  blood  up  to  3  per  cent  of  the  body 
weight  is  not  necessarily  fatal.  After  a  considerable  loss  of  blood 
there  is  a  rapid  fall  in  blood  pressure  which  in  non-fatal  cases  is 
restored  by  the  withdrawal  of  tissue  fluid  into  the  blood,  and  finally 
by  regeneration  of  the  corpuscles  in  the  blood-forming  organs. 
After  death  from  haemorrhage  the  surface  is  pale,  the  tissues  are 
lax  and  relatively  dry  from  the  absorption  of  tissue  fluids.  The 
pallor  of  the  organs  shows  how  much  their  natural  color  depends 
upon  their  blood  content.  All  the  appearances  of  anaemia  may  be 
produced  by  diminution  in  the  number  of  red  corpuscles. 

Under  normal  conditions  there  is  constant  destruction  of  the  red 
corpuscles,  as  proven  by  the  constant  formation  of  bile  pigments 
from  haemoglobin.  Where  and  how  the  destruction  is  effected  and 
the  length  of  life  of  the  corpuscle  is  uncertain.  Estimates  of  the 
amount  of  bile  pigment  produced  daily  show  that  a  daily  con- 
sumption of  one-tenth  of  the  total  haemoglobin  of  the  corpuscles 
is  required  for  the  process,  which  by  computation  makes  the  average 
life  of  the  corpuscles  approximately  ten  days. 

There  are  two  well  recognized  forms  of  anaemia.  In  one,  per- 
nicious atuzmia,  there  is  an  increased  and  continuous  destruction 
of  the  red  corpuscles  which  may  be  reduced  to  less  than  1,000,000 
per  cmm.  No  free  haemoglobin  is  found  in  the  blood  and  the 
haemoglobin  content  of  the  corpuscles  is  increased.  There  is  a 
peculiar  pale  lemon  tint  to  the  skin,  and  examination  of  the  blood 
during  life  shows  the  presence  of  nucleated  corpuscles  and  variations 
in  form  and  in  staining  reactions.  The  parenchyma tous  organs 
show  intense  fatty  degeneration  and  red  marrow  fills  shafts  of  the 
long  bones.  This  contains  large  numbers  of  nucleated  red  cells  and 
their  antecedents.  The  spleen  also  can  partake  in  this  blood  forma- 
tion and  may  contain  nucleated  red  blood  corpuscles  and  a  variable 
amount  of  erythroblastic  marrow  tissue.  Very  characteristic 
changes  are  found  in  the  liver  consisting  in  the  presence  of  an  iron- 
containing  pigment  surrounding  the  intra-  and  intercellular  bile 
capillaries.  It  is  generally  supposed  that  the  cause  of  the  disease  is 
the  formation  in  the  body  of  some  chemical  substance  which  is  toxic 
to  the  red  corpuscles  and  that  the  changes  in  the  marrow  and  spleen 
are  secondary  and  regenerative  in  character. 

Closely  allied  to  this  form  of  anaemia  is  the  secondary  anaemia 


62  PATHOLOGY 

which  may  result  from  haemorrhage,  from  prolonged  suppuration, 
other  infections  and  from  other  exhausting  conditions.  The 
changes  in  the  bone  marrow  are  not  so  marked  and  the  normal 
amount  of  red  marrow  may  not  be  increased. 

ILEMOLYSIS.  The  red  corpuscles  contain  a  considerable  amount 
of  lecithin  and  cholestrin  which  are  believed  to  have  their  chief  im- 
portance in  affecting  the  permeability  of  the  corpuscle.  In  hemol- 
ysis  the  haemoglobin  escapes  from  the  corpuscles,  is  dissolved  in 
the  serum  and  the  blood  becomes  transparent  or  laked.  This 
laking  of  the  blood,  or  haemolysis,  may  be  produced  by  lowering 
the  osmotic  pressure  of  the  plasma  or  by  the  action  of  a  number  of 
haemolytic  agents.  Some  of  these  probably  act  by  uniting  with  the 
lipoid  elements  of  the  corpuscle.  The  discharge  of  the  haemoglobin 
into  the  blood  plasma  is  called  hamoglobinamia;  the  haemoglobin 
is  in  the  form  of  methaemoglobin  and  is  excreted  by  the  kidneys, 
giving  to  these  a  peculiar  brownish  red  appearance,  and  producing 
Juzmoglobinuria. 

By  plethora  is  understood  increase  in  the  total  quantity  of  the 
blood  without  change  in  composition.  Plethora  cannot  be  experi- 
mentally produced  in  animals  by  the  transfusion  of  blood,  the  excess 
being  quickly  removed  by  blood  destruction.  In  hydramic  pleth- 
ora the  blood  plasma  alone  is  increased  in  amount.  Large  amount 
of  salt  solution  can  be  injected  into  the  blood  of  animals  but  is 
rapidly  removed  by  excretion.  In  man  the  condition  may  be  pro- 
duced by  long  standing  venous  obstruction  when  combined  with 
diminished  output  of  fluid.  In  hydmmia  there  is  a  relative  in- 
crease in  the  blood  plasma  without  increase  in  the  total  blood. 
The  condition  occurs  in  certain  cachexic  states.  In  anhydrczmia 
there  is  the  opposite  condition  of  a  relative  diminution  in  blood 
plasma;  this  occurs  particularly  in  cases  of  cholera,  the  blood 
being  drained  of  fluid  by  the  continuous  exudation  into  the  in- 
testinal canal. 

COAGULATION.  One  of  the  most  remarkable  properties  of  the 
blood  is  that  after  removal  from  the  vessels',  it  becomes  solid  or 
semi-solid  by  reason  of  fibrin  formation.  Clotting  is  due  to  the 
interaction  of  fibrinogen  calcium  salts  and  thrombin  to  form 
fibrin. 

THROMBOSIS.  The  formation  during  life,  and  from  the  con- 
stituents of  the  blood,  of  solid  masses  within  the  blood  vessels  is 


THE  PATHOLOGY  OF  THE  BLOOD         63 

called  thrombosis,  and  the  masses  so  formed  are  called  thrombi. 
Though  in  most  cases  the  process  closely  resembles  the  coagulation 
of  the  blood,  there  are  many  points  of  difference.  Thrombi  are 
always  adherent  to  the  wall  of  the  vessel  at  some  point,  and  as 
compared  with  post  mortem  clots  they  are  not  so  elastic.  Thrombi 
may  be  formed  in  any  part  of  the  circulation,  but  are  much  more 
common  in  the  veins  than  in  the  arteries.  In  the  heart  they  are 
more  common  in  the  right  side  than  in  the  left,  and  in  the  auricles 
than  in  the  ventricles.  Anatomically,  two  sorts  of  thrombi  may 
be  recognized,  the  red  and  white  thrombus.  The  red  are  formed 
of  fibrin  and  red  and  white  corpuscles.  The  clot  presents  much 
the  same  appearance  as  an  extravascular  clot,  but  the  white 
corpuscles  are  in  greater  excess  and  the  red  corpuscles  and  fibrin 
are  not  homogeneously  distributed.  The  white  thrombi  are,  for 
the  most  part,  composed  of  masses  of  blood  platelets  and  fibrin. 
If  an  opening  be  made  in  a  small  superficial  vein  of  an  animal,  the 
escape  of  blood  shortly  ceases  and  examination  shows  the  vessel 
closed  by  masses  of  blood  platelets  adhering  to  the  edges  of  the 
opening  and  extending  as  a  plug  into  the  tissue.  No  fibrin  is 
demonstrable.  If  a  vessel  be  exposed  and  injured  the  blood  platelets 
collect  at  the  site  of  injury  and  may  form  a  mass  occluding  the 
vessel.  Sections  of  large  recently  formed  thrombi  have  much  the 
same  composition;  the  masses  of  blood  platelets  form  a  network  in 
the  meshes  of  which  a  variable  amount  of  fibrin  and  corpuscles  are 
found.  The  fibrin  often  forms  immediately  around  the  blood 
plates.  The  meshwork  arrangement  of  blood  plates  probably  is 
due  to  contraction,  for  in  the  forming  thrombus  they  are  homo- 
geneously distributed.  In  small  vessels  thrombi,  not  completely 
occluding,  are  sometimes  seen,  which  are  composed  chiefly  of 
leucocytes  and  fibrin.  The  older  the  thrombi,  the  greater  are  the 
number  of  leucocytes  and  the  amount  of  fibrin,  and  the  blood 
platelets  break  up  to  form  granular  masses.  Mixed  thrombi 
composed  of  portions  of  white  and  red  may  be  found,  and  often  are 
due  to  the  entry  of  blood  into  fissures  of  a  white  thrombus.  A 
special  variety  of  thrombus  is  called  the  hyalin  thrombus.  It  is 
seen  most  frequently  in  the  capillaries  of  the  glomeruli  of  the 
kidneys  and  forms  a  constant  lesion  in  death  from  plague.  It  may 
be  produced  experimentally  in  the  kidneys  of  guinea  pigs  and 
rabbits  by  infection  with  the  diplococcus  pneumoniae.  The  hyalin 


64  PATHOLOGY 

masses  in  the  capillaries  are  due  to  the  fusion  of  red  corpuscles. 
In  these  cases  the  capillaries  elsewhere  in  the  body  may  be  entirely 
free  from  thrombi.  In  the  post  mortem  examination  of  the  tissues, 
masses  of  fibrin  and  leucocytes  often  are  found  in  the  small  vessels, 
particularly  in  the  lungs  and  it  is  difficult  to  determine  whether 
they  are  thrombi  or  post  mortem  clots. 

A  thrombus  once  formed  may  be  the  starting  point  of  a  continued, 
or  propagating,  thrombus  which  extends  along  the  thrombosed 
vessel  chiefly  in  the  direction  of  the  current  and  into  communicating 
vessels.  Such  thrombi  often  show  an  alternation  of  red  and  white; 
after  the  formation  of  the  primary  white  occluding  thrombus  a 
red  thrombus  forms  in  the  stagnating  blood  stream  and  extends  up 
to  the  point  of  entrance  of  the  next  vessel,  where  a  white  thrombus 
forms  from  the  circulating  blood  and  on  this,  when  the  vessel  is 
finally  occluded,  another  red  thrombus  is  formed.  Thrombi  which 
do  not  occlude  the  lumen  of  the  vessel  are  called  mural  thrombi 
Thrombi  are  always  rich  in  thrombin  and  it  is  difficult  to  under- 
stand why  the  blood  flowing  over  a  mural  thrombus  does  not 
further  coagulate.  It  is  held  that  the  coagulation  of  the  blood 
within  the  blood  vessels  during  life  is  prevented  by  the  presence  of 
an  antithrombin,  which  by  combining  with  prothrombin,  prevents 
the  formation  of  thrombin  and  it  is  not  unlikely  that  the  coagula- 
tion on  a  mural  thrombus  may  be  prevented  by  some  such  action. 
The  endothelium  rapidly  grows  over  such  a  thrombus  and  when 
this  takes  place  the  further  formation  is  prevented. 

The  thrombus  when  first  formed  is  moist  and  soft  in  consistency. 
By  contraction  and  extrusion  of  serum  it  becomes  more  compact, 
drier  and  more  granular  in  texture.  The  interior  of  large  thrombi, 
especially  those  formed  in  the  heart,  often  undergoes  autolysis  and 
contains  an  opaque  fluid  resembling  pus.  This,  the  puriform 
softening,  is  to  be  distinguished  from  the  true  purulent  softening 
which  takes  place  when  the  thrombus  is  infected  during  formation 
or  when  infection  extends  into  the  thrombus  from  an  infected  area 
in  the  vicinity.  Organization  of  the  thrombus  takes  place  in  the 
same  way  that  a  fibrinous  exudation  on  the  pleura  becomes  or- 
ganized. New  blood  vessels  from  the  vasa  vasorum  or  from  the 
vessels  of  the  adjoining  tissue  grow  into  it,  forming  a  network,  and 
new  connective  tissue  cells  are  formed  which  follow  the  ingrowing 
blood  vessels.  When  the  thrombus  ceases  to  extend  it  is  rapidly 


THE  PATHOLOGY  OF  THE  BLOOD          65 

covered  by  endothelium,  and  from  this  new  blood  vessels  may  be 
formed  which  extend  into  the  thrombus  and  form  communications 
with  the  vessels  which  enter  it  laterally.  In  this  way  a  circulation 
is  established  through  the  thrombus,  which  at  first  is  tortuous,  but 
later  the  vessels  become  straighter  and  then  dilated  both  from  the 
pressure  of  the  blood  within  them  and  from  the  contraction  of  the 
connective  tissue  around  them.  This  is  called  canalization  and 
the  thrombus  finally  may  be  represented  by  a  few  fibrous  bands 
across  the  vessel.  In  other  cases  the  thrombus  may  become 
calcified  by  the  deposit  of  lime  salts. 

The  cause  of  thrombus  formation  is  imperfectly  understood. 
The  two  causes  which  are  of  the  most  importance  are  injury  to  the 
endothelium  and  slowness  of  the  circulation.  The  frequent  forma- 
tion of  thrombi  in  the  course  of  infectious  diseases,  and  the  demon- 
stration of  bacteria  in  such  thrombi  shows  that  infection  plays  a 
prominent  part  in  the  production  of  endothelial  injury.  The 
importance  of  the  interaction  of  the  two  conditions  of  endothelial 
injury  and  slowness  of  circulation  acting  together  is  seen  in  the 
relative  frequency  of  thrombi  in  veins  as  compared  with  arteries. 
In  arteries  it  is  not  at  all  uncommon  to  find  areas  in  which  the  endo- 
thelium is  completely  destroyed,  and  replaced  by  an  uneven  tissue 
with  projecting  calcareous  masses  and  yet  thrombi  usually  are 
absent.  Infection  takes  place  more  easily  in  the  veins  than  in  the 
swift  current  of  the  arteries,  and  slow  circulation  also  favors  throm- 
bosis. Thrombi  are  especially  likely  to  form  in  the  pockets  behind 
the  valves,  in  which  stagnation  of  the  blood  easily  takes  place.  In 
the  heart,  thrombi  are  more  likely  to  form  in  the  auricular  append- 
ages and  between  the  muscular  bands  at  the  apices  of  the  ventricles. 
Slowness  rather  than  cpmplete  cessation  of  the  current  favors 
thrombosis.  Parts  of  a  vessel  may  be  cut  out  and  replaced  by 
devitalized  vessels  and  thrombosis  will  not  take  place,  provided 
there  is  no  stagnation  of  the  current.  Thrombi  are  more  frequent 
in  cases  of  chronic  passive  congestion  than  when  the  circulation  is 
normal ;  they  are  particularly  apt  to  occur  in  venous  plexuses,  as  at 
the  base  of  the  bladder. 

The  results  of  thrombosis  depend  chiefly  upon  the  size  and 
character  of  the  occluded  vessel.  The  immediate  effect  in  veins 
must  be  congestion  in  the  distal  veins  and  capillaries.  There 
are  usually  collaterals  which  dilate  sufficiently  to  carry  the  blood 


66  PATHOLOGY 

from  the  congested  area.  The  slow  formation  of  a  thrombus  is 
favorable  in  that  time  is  given  for  the  gradual  dilatation  of  the  col- 
lateral channels.  The  renal  vein  may  be  occluded  by  a  thrombus 
with  but  little  impairment  of  the  circulation.  When  the  collateral 
circulation  is  not  sufficient  there  may  be  chronic  congestion  and 
oedema  in  the  territory  which  the  vein  drains. 

EMBOLISM  is  the  impaction  in  some  part  of  the  vascular  system  of 
any  abnormal  material  brought  there  by  the  blood  current;  the 
impacted  material  is  an  embolus.  Such  emboli  may  be  of  solid, 
liquid  or  gaseous  substances.  Unless  some  distinguishing  epithet 
is  used  an  embolus  is  understood  to  be  a  detached  thrombus  or  part 
of  it.  In  the  various  changes  which  thrombi  undergo  the  whole 
thrombus  or  portions  of  it  can  become  detached  and  enter  into  the 
blood  current.  Emboli  are  carried  along  in  the  current  until  the 
channel  (usually  arterial)  becomes  too  small  to  permit  their  further 
passage.  Emboli  in  the  lungs  come  from  the  systemic  veins,  the 
right  heart,  or  pulmonary  artery;  those  in  the  liver  from  the  trunk, 
or  branches,  of  the  portal  vein;  those  in  the  systemic  arteries  from 
the  pulmonary  vein,  the  left  heart  or  some  artery  between  the  heart 
and  the  location  of  the  embolus.  The  course  of  an  embolus  is 
determined  by  purely  mechanical  factors,  of  which  the  most  im- 
portant are  the  size,  form  and  weight  of  the  plug,  the  direction, 
volume,  energy  of  the  carrying  blood  stream,  the  size  of  the  branches 
and  the  angles  at  which  they  are  given  off.  Emboli  coming  from 
a  source  in  the  left  heart  are  carried  more  frequently  into  the 
abdominal  aorta  and  its  branches,  than  into  the  carotid  or  sub- 
clavian  arteries.  In  rare  cases  in  which  a  congenital  opening  exists 
between  the  two  cavities  of  the  heart  an  embolus  from  a  systemic 
vein  can  pass  directly  into  the  systemic  arterial  circulation,  par- 
adoxical emboli.  Secondary  thrombi  may  form  around  emboli. 

Various  results  follow  embolism.  The  occlusion  by  a  bland 
embolus  of  an  artery  with  abundant  anastomoses,  as  in  the  volun- 
tary muscles,  the  skin,  the  uterus,  causes  no  obvious  disturbance  in 
circulation.  Sudden  death  may  result  from  the  occlusion  of  the 
trunk  or  one  of  the  main  divisions  of  the  pulmonary  artery,  or  of 
any  artery  furnishing  the  main  blood  supply  of  an  organ  essential 
for  life.  The  first  effect  of  the  occlusion  of  an  artery  supplying 
a  part  is  a  fall  in  pressure  in  all  the  vessels,  arteries,  capillaries  and 
veins,  in  the  part  supplied.  If  there  is  an  anastomosing  artery  the 


THE  PATHOLOGY  OF  THE  BLOOD         67 

blood  of  this  artery  will  flow  with  greater  rapidity  into  the  area 
of  lessened  capillary  pressure  and  in  time  the  anastomosing  artery 
becomes  so  dilated  as  to  furnish,  with  the  increased  rapidity  of 
stream,  a  sufficient  amount  of  blood.  The  occlusion  of  small 
arteries  rarely  is  disturbing  owing  to  the  abundance  of  capillary 
anastomoses  which  can  furnish  enough  blood  to  re-establish  the 
circulation.  When,  however,  the  occluded  artery  belongs  to  the 
system  of  so-called  terminal  arteries,  which  are  arteries  supplying 
definite  regions  and  without  rich  anastomoses,  the  part  undergoes 
certain  changes  which  result  in  infarction.  In  the  area  which  is 
undergoing  infarction  there  is  a  fall  in  pressure;  and  from  all  the 
anastomoses,  blood  flows  into  the  part  producing  intense  conges- 
tion, but  the  capillary  pressure  does  not  rise  to  a  sufficient  height 
to  provide  for  the  venous  outflow.  Necrosis  of  the  tissue  takes 
place  and  there  is  abundant  haemorrhage  from  the  distended  vessels. 
The  infarcted  area  usually  is  conical  or  wedge-shaped,  the  base 
being  at  the  periphery.  When  the  infarct  is  recent  the  area  is  dark 
red,  swollen  and  relatively  dry.  It  may  remain  in  this  condition, 
in  which  it  is  called  a  red  infarct,  but  in  certain  organs,  notably  in 
the  spleen  and  kidney,  the  centre  of  the  infarct  loses  its  color  by 
the  haemolysis  of  the  red  corpuscles  and  diffusion  of  the  haemoglobin 
and  becomes  of  a  pale  pink  and  later  a  yellowish  white  color. 
Around  the  white  centre  is  a  red  area  in  which  the  vessels  are 
dilated  and  the  corpuscles  in  the  tissue  preserve  their  haemoglobin. 
Leucocytes  migrate  from  the  adjoining  vessels  and  make  their  way 
for  a  certain  distance  into  the  necrosed  area.  In  certain  parts  of 
the  body,  as  in  the  brain,  the  tissue  becomes  necrotic,  and  rapidly 
undergoes  liquefaction.  In  the  liver,  due  to  the  double  blood  supply 
and  the  abundant  capillary  anastomosis,  infarction  rarely  takes 
place  as  the  result  of  embolism  in  either  the  portal  veins  or  in  the 
hepatic  artery.  In  the  lung  under  normal  conditions  of  the  circu- 
lation infarction  does  not  follow  occlusion  of  small  branches  of  the 
pulmonary  artery.  This  is  due  mainly  to  the  enormous  extent  of 
the  capillary  anastomosis  which  brings  sufficient  blood  into  the 
part  to  establish  the  circulation.  In  case,  however,  there  is  passive 
congestion  with  an  increased  pressure  in  the  pulmonary  veins,  the 
circulation  by  capillary  anastomosis  is  not  sufficient  to  overcome 
the  venous  pressure  and  infarction  takes  place.  Whether  or  not 
infarction  takes  place  must  depend  in  part  upon  the  character  of 


68  PATHOLOGY 

the  tissue  and  its  resistance  to  lack  of  blood  supply.  If  the  tissue 
be  one  which  easily  undergoes  necrosis  the  rapid  occurence  of  this 
will  bring  about  the  conditions  for  infarction  before  there  is  time 
for  the  establishment  of  the  collateral  circulation. 

PARENCHYMATOUS  EMBOLI  are  due  to  the  entry  of  cells  of  organs 
into  the  circulation.  This  has  been  described  more  frequently  in 
connection  with  the  cells  of  the  liver  than  of  any  other  organ.  In 
consequence  of  severe  crushing  injuries  of  the  liver,  portions  of 
tissue  may  be  forced  into  the  hepatic  veins  and  be  carried  away  as 
emboli.  The  large  cells  of  the  bone  not  infrequently  enter  into  the 
blood  and  may  be  found  as  emboli  in  the  capillaries  of  the  lung.  It 
more  commonly  occurs  in  children  than  in  adults.  Almost  invari- 
ably, in  cases  of  pregnancy,  the  syncytial  giant  cells  in  the  placental 
sinuses  enter  the  circulation  and  occlude  without  harm,  small  vessels 
in  the  lungs.  The  cells  of  malignant  tumors  often  enter  the  circula- 
tion and  may  be  carried  into  various  places  producing  metastases. 

FAT  EMBOLISM.  At  the  temperature  of  the  body  fat  is  fluid  and 
in  case  of  injury,  particularly  crushing  injuries,  in  which  both  fat 
cells  and  veins  are  ruptured  the  fluid  fat  may  enter  into  the  circula- 
tion. This  most  readily  takes  place  in  such  injuries  of  bones. 
The  fat  then  is  carried  into  and  obstructs  the  capillaries  of  the  lungs. 
When  a  large  amount  enters  the  circulation  it  may  pass  through  the 
lung  capillaries  and  enter  into  the  systemic  circulation  where  it  is 
most  often  found  in  the  vessels  of  the  glomeruli  of  the  kidneys. 
The  importance  of  fat  embolism  formerly  was  greatly  overrated. 
With  the  abundant  capillary  anastomosis  in  all  organs,  many 
capillaries  may  be  obstructed  with  little  harm.  Death  may  follow 
when  the  process  is  very  extensive  and  great  numbers  of  capillaries 
in  the  lungs  and  brain  become  occluded. 

AIR  EMBOLISM.  When  air  in  a  considerable  amount  enters 
suddenly  into  the  circulation  it  may  obstruct  it  by  forming  emboli 
in  the  capillaries  and  by  interference  with  the  action  of  the  heart. 
Cases  of  sudden  death  have  been  attributed  to  this  and  the  presence 
of  gas  in  the  vessels  after  death  was  considered  evidence  of  the 
entrance  of  air.  Since  it  has  become  known  that  the  presence  of 
gas  in  the  vessels  is  almost  invariably  due  to  the  action  of  the 
bacillus  aerogenes  capsulatus  or  to  the  surgical  opening  of  large 
veins  in  the  area  of  negative  pressure  these  cases  have  become  very 
infrequent. 


THE  PATHOLOGY  OF  THE  BLOOD          69 

EXPERIMENTS.  In  the  experimental  work  on  blood,  particular  at- 
tention should  be  given  to  the  study  of  human  blood.  The  students 
can  do  this  best  working  in  pairs.  The  finger  tip  or  ear  lobule  should 
be  cleansed  with  soap  and  water,  followed  by  alcohol  and  dried  with 
a  clean  pledget  of  gauze  or  cotton.  A  puncture  about  5  mm.  deep 
should  be  made  with  a  blood  lancet,  needle  or  a  single  point  of  a 
steel  pen.  A  drop  may  be  placed  on  a  warm  slide,  covered  with 
a  coverslip  and  studied  fresh  to  observe  the  natural  form  of  the 
corpuscles,  the  rouleaux  and  the  amoeboid  activity  of  the  leuko- 
cytes. For  making  stained  specimens  two  carefully  cleaned  cover- 
slips  are  used.  A  small  drop  of  blood  is  placed  on  one  and  the  other 
dropped  on  it  so  that  the  corners  remain  free  for  grasping.  As 
soon  as  the  drop  of  blood  spreads  out  the  upper  cover  is  rapidly 
slid  off  the  lower,  the  two  dried  and  stained,  either  with  eosin 
methylene  blue  or  some  of  the  combined  stains  such  as  the  Wright, 
Leishmann  or  Romanowsky  stains. 

For  the  study  of  some  especial  phases  of  blood  destruction, 
anaemia  and  haematogenous  jaundice,  the  following  experiments 
are  of  value.  The  haemolytic  effect  of  the  intravenous  injection 
into  a  rabbit  of  a  solution  of  o.ooi  gram  dried  rattlesnake  venom 
in  salt  solution.  Place  the  animal  in  a  metabolism  cage,  note 
the  haemoglobinuria  and  at  autopsy  study  the  haemoglobinaemia 
and  the  general  tissue  changes.  In  contrast  the  subcutaneous 
injection  of  o.ooi  gram  cantharadin  in  acetic  ether  produces,  in 
the  rabbit,  haematuria  and  somewhat  different  tissue  changes, 
especially  in  the  kidney.  Blood  destruction,  haemaglobinuria  and 
jaundice  can  be  produced  by  the  intravenous  injection  of  a  specific 
immune  serum.  This  is  done  in  the  cat,  usually  in  amounts  of 
0.5  c.c.  immune  serum  to  the  kilo  of  body  weight.  Autopsy  at 
the  end  of  two  or  three  days  should  include  careful  examination  of 
the  spleen  and  lymph  nodes  for  phagocytosis  of  destroyed  blood 
corpuscles,  of  the  liver  for  focal  necrosis  and  of  the  kidneys  for 
nephritis.  A  similar  experiment  in  the  recently  splenectomized 
animal  shows  the  most  marked  phagocytosis  of  red  blood  cells 
in  the  lymph  nodes. 

Haemolysis  in  vitro  can  be  determined  as  follows:  Place  in  each 
of  4  test  tubes  i  c.c.  5  per  cent  suspension  cat's  erythrocytes  in 
salt  solution.  Add  to  test  tube  i,  2  c.c.  salt  solution;  to  test  tube 
2,  o.i  c.c.  guinea  pig  serum  (complement)  and  1.9  c.c.  salt  solution; 


70  PATHOLOGY 

to  test  tube  3,  i  c.c.  dilution  of  specific  immune  serum  (amboceptor) 
which  has  been  inactivated  by  a  temperature  of  56°  C.  for  one-half 
hour;  and  to  test  tube  4,  o.i  c.c.  complement,  0.9  c.c.  salt  solution, 
and  i  c.c.  amboceptor  dilution.  Incubate  for  one  hour  at  37°  C. 
and  note  that  the  presence  of  both  amboceptor  and  complement 
is  necessary  for  haemolysis. 


70  a 


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yo  d 


yo  e 


70  f 


7°  g 


70  h 


701 


yo  k 


70 1 


THE  PATHOLOGICAL  ANATOMY  OF  THE  HEART 
AND  THE  BLOOD  VESSELS 

THE  HEART  may  be  regarded  as  a  greatly  modified  blood  vessel  of 
the  arterial  type,  the  endocardium  corresponding  to  the  intima,  the 
myocardium  to  the  media  and  the  epicardium  to  the  adventitia. 
The  endocardium,  lined  with  the  endothelial  cells  common  to  the 
vascular  tube,  is  a  non-vascular  connective  tissue  membrane  which 
contains  a  varying  but  small  amount  of  elastic  tissue  and  non- 
striated  muscle  cells.  The  valves  are  duplicatures  of  the  endo- 
cardium with  marked  development  of  elastic  fibres  and  with  a 
considerable  amount  of  nonstriated  muscle.  The  myocardium  is 
composed  of  short  cylindrical,  striated  muscle  cells  arranged  in 
bundles.  The  cells  branch  to  a  varying  degree.  The  branches  of 
different  cells  anastomose  and  vary  in  size,  the  largest  being  found 
in  the  ventricles.  Each  cell  contains  in  the  centre  an  oval  vesicular 
nucleus  surrounded  by  a  small  amount  of  sarcoplasm,  which 
usually  contains  a  small  amount  of  brown  pigment  greatly  increased 
in  certain  atrophic  conditions.  The  epicardium  is  composed  of 
connective  tissue  and  elastic  fibres  and  its  surface  is  covered  with 
flat  mesothelial  cells.  The  larger  branches  of  the  coronary  arteries 
ramify  in  the  epicardium.  Fat  tissue  in  varying  amount  occurs 
beneath  the  epicardium,  especially  on  the  right  side  of  the  heart 
and  at  the  junction  of  auricles  and  ventricles.  The  heart  is  en- 
closed completely  in  the  pericardial  sac,  the  latter  being  attached 
around  the  great  vessels.  The  parietal  pericardium,  although 
thicker,  has  the  same  general  structure  as  the  epicardium.  The 
parietal  pericardium  has  an  abundant  blood  supply  and  is  in  close 
topographical  relation  with  the  pleurae  the  mediastina  and  the 
peritoneum.  Unlike  other  blood  vessels  the  inner  surface  of  the 
heart  is  irregular;  the  surface  in  contact  with  the  blood  is  very 
large.  The  myocardium  receives  a  large  blood  supply  from  the 
two  coronary  arteries.  There  is  limited  anastomosis  between  the 
different  arterial  branches,  the  extent  varying  greatly  in  different 
individuals.  The  capillary  circulation  in  the  myocardium  is 

71 


72  PATHOLOGY 

greater  than  in  any  other  muscular  tissue  of  the  body.  The  size 
of  the  heart  varies  considerably,  being  influenced  by  age,  sex,  height, 
muscular  development  and  occupation  of  the  individual.  The 
average  weights  are  20  grams  in  the  newborn,  300  grams  between 
ages  of  thirty  and  fifty  years,  increasing  to  330  grams  at  the  age  of 
sixty-five;  the  weight  of  the  heart  of  the  female  from  five  years  of 
age  and  upward  is  somewhat  less,  averaging  between  the  ages  of 
twenty  and  fifty  years,  270  grams. 

PERICARDIUM.  The  most  common  pathological  condition  is  acute 
pericarditis,  due  either  to  an  extension  of  infection  from  the  neigh- 
boring tissues  or  to  infectious  organisms  carried  by  the  blood  or 
lymphatic  vessels. 

The  exudation  may  be  serous,  sero-fibrinous,  purulent,  fibrino- 
purulent  or  hemorrhagic,  depending  essentially  upon  the  character 
of  the  infectious  agent.  Fibrin  almost  invariably  is  present,  both 
as  masses  in  the  fluid  exudate  and  as  a  deposit  on  the  surface. 
In  small  amounts  it  may  produce  merely  a  clouding  of  the  surface ; 
when  abundant  it  forms  shaggy  masses  covering  both  parietal 
and  visceral  pericardium  and  often  presents  peculiar  rolls  and  a 
network  due  to  the  friction  of  the  opposing  surfaces.  The  amount 
of  the  fluid  exudation  may  be  very  considerable,  occasionally 
reaching  1000  c.c.  Usually  healing  takes  place  by  organization  of 
the  exudate  with  obliteration,  either  partial  or  complete,  of  the 
pericardial  cavity  by  the  union  of  the  opposed  surfaces.  Where 
the  exudation  has  been  very  extensive,  thick  masses  of  dense 
cicatricial  tissue  may  result  from  the  organization.  In  association 
with  the  pericarditis  there  may  be  pleuritis  with  obliteration  of  the 
pleural  cavities  and  inflammation  of  mediastina  resulting  in  forma- 
tion of  dense  masses  of  connective  tissue.  The  special  forms  of 
pericarditis  due  to  special  infectious  agents  will  be  considered  under 
the  infections.  Small  circumscribed  haemorrhages  (ecchymoses)  in 
the  pericardial  tissue,  especially  in  the  epicardium,  are  found  in 
death  from  suffocation,  in  various  intoxications  and  in  many  of  the 
infectious  diseases.  In  inflammation  also,  especially  when  the 
exudation  has  a  haemorrhagic  character,  small  epicardial  haemor- 
rhages often  are  seen.  Extensive  haemorrhage  into  the  pericardial 
cavity,  apart  from  that  resulting  from  perforating  wounds  of  the 
heart,  is  due  to  rupture  of  the  heart  or  the  great  vessels  often  pre- 
ceded by  aneurysm  formation.  There  may  be  large  accumulation 


THE  PATHOLOGICAL  ANATOMY  OF  THE  HEART,  ETC.  73 

of  serous  fluid  in  the  pericardial  cavity  (hydropericardium),  due  to 
disturbances  in  the  circulation. 

MYOCARDIUM.  Various  forms  of  degeneration  occur  in  the  myo- 
cardium. Cloudy  swelling  occurs  in  most  of  the  acute  infectious 
diseases,  especially  when  accompanied  by  high  fever.  Fatty  de- 
generation is  common  and  may  not  produce  any  macroscopic 
changes.  It  rarely  is  diffuse  affecting  equally  all  parts  of  the  heart, 
but  usually  is  more  marked  beneath  the  endocardium,  especially 
in  the  left  ventricle  and  in  the  papillary  muscles,  than  elsewhere 
Fat  infiltration  of  the  heart  may  be  a  pathological  condition  due 
to  growth  of  the  epicardial  fat  into  the  myocardium,  pushing  the 
muscle  fibres  aside  and  producing  atrophy.  Necrosis  usually  is 
the  result  of  interference  with  the  coronary  circulation,  or  takes 
place  around  bacterial  emboli.  Rarely,  a  form  of  hyalin  degenera- 
tion and  necrosis  of  single  fibres  is  seen  in  infectious  diseases  as  the 
result  of  toxin  action.  A  peculiar  form  of  degeneration,  consisting 
in  destruction  of  the  fibrillae  in  the  centre  of  the  fibre,  sometimes  is 
seen  in  diphtheria  and  in  fibres  which  have  become  hypertrophied. 
Extensive  lesions  are  produced  in  the  heart  by  impairment  in  the 
blood  supply,  due  to  lesions  of  the  coronary  arteries.  The  lumina 
of  the  chief  stems  or  their  branches  may  be  obstructed  by  arterio- 
sclerosis, thrombosis  or  embolism.  Necrosis  may  result,  sometimes 
followed  by  softening  and  perforation  of  the  heart  and  more  rarely 
by  haemorrhagic  infarction.  The  descending  branch  of  the  left 
coronary  artery  is  most  frequently  affected.  Although  the  myo- 
cardium must  be  regarded  as  relatively  susceptible  to  the  action 
of  toxic  substances,  as  shown  by  the  frequency  of  degenerations, 
acute  bacterial  infections  are  comparatively  rare.  These  may  be 
produced  by  infection  from  the  blood  stream  or  by  the  extension  of 
an  endocardial  infection.  Small  abscesses  may  occur  in  staphyl- 
ococcus  aureus  septicaemia  and  miliary  tubercles  are  rarely  found. 
Focal  accumulations  of  cells  belonging  to  the  lymphoid  type  may 
be  found  in  the  acute  infectious  diseases  particularly  in  acute 
rheumatic  fever. 

The  minor  degrees  of  the  various  degenerations  of  the  myo- 
cardium may  be  recovered  from,  leaving  no  trace.  In  necrosis  and 
the  more  serious  injuries  the  degenerated  fibres  are  absorbed  and 
substituted  by  the  formation  of  connective  tissue. 

FIBROUS  MYOCARDITIS,  like  the  degenerations,  may  be  focal 


74  PATHOLOGY 

affecting  only  small  areas  of  the  heart,  or  the  entire  myocardium 
may  contain  numbers  of  small  cicatricial  streaks.  The  substituted 
connective  tissue  has  not  the  resistance  of  the  muscular  tissue  and 
the  area  affected  may  gradually  give  way  before  the  blood  pressure 
and  a  local  dilatation  or  aneurysm  of  the  heart  wall  may  result. 
Corresponding  to  the  frequency  of  disease  of  the  descending  branch 
of  the  left  coronary,  the  most  extensive  areas  of  fibrous  myocarditis, 
followed  by  dilatation,  are  found  at  the  apex  of  the  left  ventricle. 
In  and  around  the  areas  of  fibrous  myocarditis,  both  greatly  atro- 
phied and  greatly  hypertrophied,  muscle  fibres  may  be  seen.  Parts 
of  the  myocardium  which  are  of  especial  functional  importance 
may  be  affected,  such  as  the  fibre  bundle  of  His,  with  a  resulting 
impairment  of  the  association  of  auricular  and  ventricular  con- 
traction. 

HEART  HYPERTROPHY.  The  heart,  like  the  other  muscles  and 
organs  of  the  body,  has  great  reserve  force,  by  reason  of  which  it 
is  enabled  suddenly  to  perform  more  work  than  ordinarily  is  called 
for.  When  there  is  a  frequently  repeated  or  permanent  demand  for 
increased  function  made  upon  the  heart,  the  muscle  hypertrophies. 
Hypertrophy  is  due  most  frequently  to  obstruction  of  the  valvular 
orifices  and  affects  the  part  of  the  heart  concerned  in  forcing  the 
blood  through  the  obstructed  orifice.  Hypertrophy  usually  is 
accompanied  by  dilatation,  which  is  as  much  a  part  of  the  adapta- 
tion as  the  hypertrophy,  for  in  most  of  the  conditions  which  are 
followed  by  hypertrophy  the  cardiac  cavity  involved  must  accomo- 
date  a  greater  amount  of  blood.  The  weight  of  the  hypertrophied 
heart  may  be  increased  up  to  more  than  three  times  the  normal. 

ENDOCARDIUM.  The  endocardium  is  more  subject  to  infection 
than  the  intima  of  any  other  vessel  in  the  body.  This,  to  a  large 
extent,  is  due  to  irregularity  of  surface,  and  to  the  action  of  the 
valves,  which  by  contact  and  friction  of  surfaces  mechanically  favor 
the  access  of  infectious  organisms.  However  much  are  the  varia- 
tions in  the  anatomical  appearances  of  the  lesions,  and  however 
much  the  causes  vary,  the  mode  of  production  of  the  lesions  is  the 
same.  Anatomically  two  main  types  are  recognized  endocarditis 
•oerrucosa  and  endocarditis  ukerosa.  In  both,  the  process  is  essen- 
tially an  infectious  thrombosis.  The  most  common  lesions  in  the 
verrucose  form  cc  r.sist  in  the  formation  of  warty  or  papillary  masses 
along  the  line  of  closure  of  the  valves.  They  may  be  so  small 


THE  PATHOLOGICAL  ANATOMY  OF  THE  HEART,  ETC.  75 

and  transparent  as  to  be  recognized  with  difficulty  by  the  naked 
eye  or  may  form  large,  irregular  masses  a  centimeter  or  more  in 
diameter.    On  section,  the  mass  has  the  character  of  a  blood  plate 
thrombus  with  a  varying  admixture  of  fibrin  and   corpuscles. 
Bacteria,  in  enormous  numbers  and  taking  the  form  of  colonies, 
often  are  found  in  the  thrombi.    At  the  point  of  attachment  the 
endothelium  is  absent  and  there  is  a  superficial  necrosis  of  the 
valvular  tissue  with  infiltration  of  leucocytes  and  proliferation  of 
the  cells  at  the  edge  of  the  necrotic  tissue.    In  the  more  severe 
types  of  infection  there  may  be  extensive  necrosis  and  no  evidence 
of  reaction  on  the  part  of  the  tissue.    The  leucocytes  in  the  throm- 
bus usually  are  broken  down,  forming  masses  of  nuclear  detritus. 
The  milder  degrees  of  this  form  of  endocarditis  are  common  and 
recovery  can  take  place  without  the  production  of  permanent 
functional  injury,  only  a  slight  thickening  of  the  valve  resulting. 
When  the  thrombus  formation  is  more  extensive,  organization 
takes  place  and  the  thrombus  is  replaced  by  granulation  tissue 
which  finally  results  in  great  cicatricial  thickening  of  the  valve  and 
the  production  of  an  uneven  often  papillary  surface.    The  forma- 
tion of  cicatricial  tissue  may  extend  for  a  distance,  involving,  in  the 
case  of  the  mitral  valve,  the  chordae  tendineae  in  the  process.    The 
valves  may  be  shortened  by  the  formation  and  contraction  of  the 
cicatricial  tissue,  they  may  grow  together  at  their  opposed  edges, 
and  by  the  contraction  of  the  chordae  tendineae,  the  edges  of  the 
mitral  valve  may  be  drawn  down  into  the  ventricle  in  the  shape  of 
a  funnel.    There  frequently  is  a  deposit  of  lime  salts  in  the  cicatricial 
tissue,  changing  the  valve  into  a  hard,  unyielding  mass.    There  is 
a  great  liability  to  recurrent  attacks,  due  to  the  persistence  of  the 
infectious  agents  in  the  body  and  to  the  increased  opportunity  given 
for  the  lodgment  of  bacteria  by  the  great  irregularity  of  surface. 
In  ulcerative  endocarditis,  the  cause  of  which  is  most  frequently 
the  pyogenic  bacteria,  particularly   the  staphylococcus  aureus, 
there  is  extensive  softening  and  destruction  not  only  of  the  thrombus 
but  of  the  necrotic  tissue  of  the  valve.    Valves  may  be  perforated 
or  entirely  destroyed.      Although  acute   endocarditis   generally 
affects  the  valves,  other  parts  of  the  endocardium  may  be  affected 
primarily  and  the  process  may  extend  from  the  affected  valves  to 
the  adjacent  surfaces;    particularly  is  this  true  in  the  ulcerative 
form,  in  which  there  may  be  extensive  necrosis,  abscess  formation 


76  PATHOLOGY 

and  ulceration  in  the  myocardium.  These  various  forms  of  endo- 
carditis, particularly  the  ulcerative,  are  a  frequent  source  of  emboli 
in  the  arterial  system.  Endocarditis  is  much  more  frequent  in  the 
left  than  in  the  right  side  of  the  heart  and  the  mitral  valve  is  some- 
what more  frequently  attacked  than  is  the  aortic. 

In  consequence  of  the  lesions  produced  the  action  of  the  valves 
is  interfered  with.  By  shortening  and  contraction  they  may  no 
longer  close  the  orifices,  insufficiency,  or  by  their  induration  and  the 
union  of  adjoining  edges  they  may  narrow  the  orifices,  stenosis. 
In  most  cases  both  stenosis  and  insufficiency  result.  Valvular 
aneurysms  may  result  from  partial  destruction,  the  thin  portion 
of  the  valve  gradually  dilating  under  the  blood  pressure. 

VEINS.  They  are  more  frequently  the  seat  of  infections  than  are 
the  arteries  because  of  the  greater  slowness  of  the  blood  current,  the 
relatively  greater  surface  and  the  irregularities  of  surface  due  to 
the  valves.  Acute  inflammation  of  the  veins,  phlebitis,  is  due  to 
infection  either  from  the  blood  stream  or  to  extension  of  a  neigh- 
boring infective  process,  and  leads  to  the  formation  of  thrombi. 
By  varicose  veins  is  understood  dilatation  of  the  lumen  usually  with 
elongation  of  the  vessel  and  thickening  of  the  walls.  It  is  most 
frequent  in  the  subcutaneous  veins  of  the  lower  extremities,  which 
appear  as  thick  tortuous  or  worm-like  cords  beneath  the  skin. 
On  section,  the  thickened  wall  is  formed  chiefly  of  cicatricial  tissue 
and  the  lumen  is  irregular.  Both  occluding  and  mural  thrombi 
are  not  uncommon  and  by  their  organization  add  to  the  amount  of 
cicatricial  tissue.  The  condition  seems  to  be  due  to  some  congenital 
weakness  or  imperfection  in  formation  of  the  wall,  added  to  by 
increased  venous  pressure. 

ARTERIES.  The  frequent  and  important  pathological  changes 
in  arteries  are  due  primarily  to  imperfections  in  structure.  The 
structure  is  admirable  for  its  functions.  The  combination  of  smooth 
muscle  and  elastic  tissue  in  the  large  conducting  arteries  gives  the 
necessary  components  of  strength  and  elasticity,  and  the  pre- 
dominating muscular  tissue  in  the  small  distributing  arteries,  under 
the  control  of  the  vaso  motor  nerves,  provides  for  the  necessary 
regulation  of  local  blood  supply.  There  is  a  degree  of  functional 
adaptation  beyond  this,  for  the  artery  can  both  enlarge  by  growth, 
as  is  seen  in  the  increase  in  size  of  anastomosing  branches  after  the 
closure  of  a  main  stem,  or  diminish  in  calibre,  this  taking  place  in 


THE  PATHOLOGICAL  ANATOMY  OF  THE  HEART,  ETC.   77 

extreme  cases  by  the  formation  of  a  new  artery  with  perfect  coats 
inside  of  the  old.  Newly  formed  blood  vessels  can  undergo  a 
differentiation  into  arteries  and  veins  as  in  the  embryo.  There  is 
a  definite  regulation  between  blood  supply  and  blood  demand, 
which  regulation  when  it  passes  beyond  the  limits  of  the  physiologi- 
cal contraction  and  expansion  is  effected  by  growth.  It  seems 
probable  that  such  regulation  is  not  perfect  and  that  it  carries  with 
it  a  loss  of  the  power  of  adaptation.  The  greatly  enlarged  hyper- 
trophied  heart  has  enlarged  coronary  arteries,  but  the  frequent 
association  of  interstitial  lesions  with  the  hypertrophy  shows  a 
greater  vulnerability  of  the  tissue,  which  may  be  due,  in  part  at 
least,  to  an  imperfect  adaptation  of  the  blood  supply  to  the  greater 
needs  imposed  upon  it.  The  imperfect  character  of  the  structure 
of  the  arterial  wall  is  made  manifest  by  its  nondurability,  which  is 
not  counterbalanced  by  its  capacity  for  repair.  Various  tissues 
are,  in  a  complex  way,  united  in  the  arterial  wall,  and,  in  regenera- 
tion, a  complex  architectural  structure  is  not  perfectly  reproduced. 
New  and  perfect  arteries  frequently  are  formed,  but  repaired 
arteries  always  are  imperfect.  The  nutrition  of  the  wall  is  not 
amply  provided  for;  save  in  the  ascending  aorta  there  are  no  blood 
vessels  in  the  media,  the  nutrition  being  effected  through  the  intima 
and  the  comparatively  few  vessels  of  the  adventitia.  Of  all  the 
tissues  of  the  body  the  arteries  are  the  most  prone  to  the  degenera- 
tions associated  with  age.  Perfectly  normal  arteries  rarely  are 
found  in  individuals  over  forty. 

ARTERIO-SCLEROSIS.  The  most  common  pathological  condition 
found  in  the  arteries  is  arterio-sclerosis.  It  appears  hi  many  forms, 
affecting  sometimes  circumscribed  areas  only,  at  others  the  entire 
circumference  of  the  vessels ;  it  may  be  a  general  process  affecting, 
to  a  greater  or  less  extent,  all  the  arteries  of  the  body,  or  may  be 
confined  to  a  single  arterial  system.  It  plays  a  prominent  part  in 
most  of  the  organic  diseases,  especially  those  occurring  after  the 
age  of  fifty  and  is  the  most  prominent  of  the  senile  changes.  It 
consists  essentially  of  circumscribed  or  diffuse  thickening  of  the 
intima  associated  with  degeneration  of  both  intima  and  media. 
The  first  change  is  degeneration,  which  is  followed  by  dilatation 
of  the  vessel  and  new  formation  of  tissue  in  the  intima  at  the  point 
of  dilatation.  The  primary  change  is  a  fatty  degeneration  of  the 
elastic  and  connective  tissue  of  both  intima  and  media.  Such  areas 


78  PATHOLOGY 

appear  as  opaque,  white  or  yellow  streaks  extending  longitudinally. 
The  degenerated  elastic  fibres  not  infrequently  break  and  their 
edges  curl  up.  The  muscular  tissue  also  shares  in  the  degenera- 
tion and  the  cells  become  fatty  and  hyalin.  The  thickening  of 
the  intima  appears  later  and  may  take  the  form  of  projecting 
plaques  which  seem  to  be  laid  on  th»  surfac.  These  are  composed 
of  dense  sclerotic  fibrous  tissue  in  which  a  great  number  of  elastic 
fibres  and  a  few  muscle  fibres  are  intermingled.  The  cells  vary  in 
number  and  examination  shows  a  large  amount  of  fat  in  both  the 
cells  and  tissue.  The  tissue  formation  is  densest  on  the  inner  side 
and  below  this  is  an  area  containing  numbers  of  lymphoid  and 
epithelioid  cells,  the  latter  usually  being  swollen  and  filled  with  fat 
lying  in  a  homogeneous  or  hyalin  tissue.  Connective  tissue  forma- 
tion in  the  media  also  follows  the  degeneration,  but  there  is  no 
elastic  tissue  formation.  Sections  of  the  small  arteries  show  the 
same  condition  of  degeneration  and  in  some  cases  a  complete  dis- 
appearance of  the  media;  uneven  dilatation  of  the  vessel  and  new 
formation  of  tissue  in  the  intima  is  most  marked  at  the  site  of 
the  greatest  dilatation.  Rarely,  even  in  the  small  arteries,  do  the 
changes  uniformly  affect  equally  the  entire  circumference.  The 
fatty  degeneration  in  the  thickened  plaques  increases  and  softening 
takes  place,  resulting  in  the  formation  of  an  opaque  white  fluid  in 
which  cholestrin  and  fatty  acid  crystals  may  be  found.  Calcifica- 
tion in  such  areas  is  a  common  process,  or  the  softening  may  con- 
tinue and  the  area  finally  break  through  into  the  interior  of  the 
vessel  producing  an  atheromatous  ulcer.  In  the  more  strictly  senile 
forms  of  arterio-sclerosis  the  process  is  more  diffuse,  the  connective 
tissue  thickening  is  less  marked  and  the  degeneration  and  calci- 
fication more  evident.  Calcification  is  more  marked  in  the  ab- 
dominal aorta  and  in  the  arteries  of  the  lower  extremities  than 
elsewhere.  It  occurs  first  in  plaques  which  finally  involve  the 
entire  circumference,  and,  uniting,  change  the  arteries  into  rigid 
calcareous  tubes.  Dilatation  of  the  entire  artery  takes  place  with 
lengthening  giving  rise  to  tortuosities  which  are  particularly  evident 
in  the  splenic  artery.  Although  the  media  normally  is  devoid  of 
vessels,  vessels  are  usually  found  in  the  degenerated  tissue  below 
the  thickened  media. 

Much  the  same  conditions  as  in  the  aorta  may  be  produced  in 
the  cardiac  valves  resulting  in  thickening  and  contraction  of  the 


THE  PATHOLOGICAL  ANATOMY  OF  THE  HEART,  ETC.  79 

tissue  and  calcification.  This  most  frequently  affects  the  aortic 
valves  and  the  aortic  leaflet  of  the  mitral  valve.  The  stenosis 
of  the  aortic  valves  due  to  the  projection  and  frequent  adhesion 
of  the  calcified  leaflets  may  be  extreme. 

Syphilitic  arterio-sclerosis.  This  is  a  special  form  of  sclerosis 
which  occurs  chiefly  in  the  ascending  aorta  and  arch,  but  may  be 
combined  with  the  ordinary  type  of  arterio-sclerosis.  The  essential 
lesions  are  in  the  media  and  consist  in  the  formation  of  cellular 
granulation  tissue  with  extensive  necrosis  and  degeneration.  In 
consequence  of  the  necrosis  the  tissue  is  converted  into  a  granular 
mass  without  nuclei  and  in  which  the  wall  lamination  is  still  visible. 
Breaks  and  fractures  of  this  tissue  are  common  and  into  these 
rents  the  granulation  tissue  with  its  newly  formed  vessels  extends. 
Giant  cells  often  are  found  in  the  tissue  and  there  may  be  definite 
gummata  with  surrounding  necrosis.  The  intima  is  greatly 
thickened  and  presents  a  rough  nodular  surface  often  with  definite 
cicatrices.  The  process  may  involve  the  entire  circumference  of 
the  vessel  or  may  appear  in  patches.  The  treponema  pallidium  is 
found  in  the  lesions.  The  syphilitic  process  here  is  very  similar  to 
that  of  the  endarteritis  syphilitica  of  the  small  arteries  particularly 
those  of  the  brain  and  which  often  leads  to  complete  closure  of  the 
lumen. 

Periarteritis  nodosa  appears  in  the  form  of  nodules  on  the  small 
arteries;  these  show,  on  section,  cellular  infiltration  of  the  wall  with 
degeneration  of  elastic  and  muscular  tissue. 

In  the  course  of  acute  infectious  diseases  a  peculiar  form  of  endar- 
teritis often  is  seen,  more  frequently  in  the  arteries  of  the  pia  mater 
and  the  spleen.  This  consists  in  a  proliferation  of  the  endothelial 
cells,  often  forming  festoons  projecting  into  the  vessel  and  covered 
by  flat  endothelium.  A  similar  condition  is  found  less  frequently 
in  veins.  It  is  uncertain  whether  or  not  this  condition  is  associated 
with  endarteritis  obliterans,  in  which  the  calibre  of  the  artery  is 
narrowed  by  formation  of  connective  tissue  in  the  intima  and  which 
is  not  associated  with  degeneration  of  the  media.  The  condition 
is  to  be  distinguished  from  the  compensatory  narrowing  of  an  artery 
which  takes  place  when  the  vascular  territory  which  it  supplies 
is  reduced.  In  endarteritis  obliterans  the  connective  tissue  may 
appear  at  one  point  or  affect  the  entire  circumference.  It  is  not 
at  all  unlikely  that  the  condition  often  is  due  to  the  formation  of 


8o  PATHOLOGY 

mural  thrombi  followed  by  complete  organization.  More  rarely 
small  foci  of  necrosis  are  found  which  begin  in  the  intima  and  ex- 
tend into  the  media.  A  small  loss  of  substance  results  on  which 
fibrin  may  be  deposited  and  which  later  becomes  covered  with 
endothelium.  The  condition  is  not  uncommonly  found  in  the 
arteries  of  the  submucosa  of  the  intestine,  in  bacillary  dysentery 
and  in  the  arteries  of  the  lymphoid  follicles  in  typhoid  fever.  It  is 
not  impossible  that  such  lesions  may  form  the  starting  point  of 
certain  aneurysms. 

ANEURYSM.  This  is  a  cavity  communicating  with  the  lumen  of 
an  artery  and  formed  in  whole  or  in  part  by  dilatation  of  the  wall. 
The  formation  of  an  aneurysm  is  due  to  degeneration  of  the  arterial 
wall  which  becomes  weakened  at  the  area;  the  compensatory  for- 
mation of  connective  tissue  is  not  sufficient  to  withstand  the  blood 
pressure  and  dilatation  takes  place.  Various  forms  of  aneurysm 
are  distinguished.  An  artery  may  be  dilated  over  a  large  area, 
forming  a  diffuse  aneurysm,  or  the  dilatation  may  involve  the  entire 
circumference  of  the  artery  for  a  certain  distance  producing  a 
spindle-form  aneurysm.  The  most  common  and  most  typical  is 
the  sacular  aneurysm,  in  which  the  dilatation  occurs  in  a  circum- 
scribed area;  the  sac  so  formed  is  circumscribed  and  communicates 
with  the  lumen  of  the  artery  by  an  opening  which  usually  is  smaller 
than  the  cavity  of  the  sac.  Aneurysms  may  be  single  or  multiple. 
In  certain  cases  of  arterio-sclerosis  it  is  not  uncommon  to  find 
numerous  small  sacs  along  the  course  of  the  artery  (cirsoid  aneu- 
rysm). 

Where  the  dilatation  takes  place  there  has  been  extensive  de- 
generation of  the  arterial  wall  followed  by  connective  tissue  forma- 
tion, so  that  the  normal  wall  of  the  vessel  is  not  represented  in  the 
wall  of  the  aneurysm.  Where  the  sac  is  given  off  from  the  artery 
the  elastic  tissue  of  the  media  passes  for  a  variable  distance  into  the 
aneurysmal  wall.  Sections  made  elsewhere  may  show  fragments 
of  elastic  and  muscular  tissue,  but  the  wall  is  composed  principally 
of  dense  connective  tissue,  the  fibres  of  which  are  fused  and  hyalin. 
The  internal  surface  is  irregular  and  covered  in  whole  or  in  part  by 
endothelium.  Aneurysms  almost  invariably  contain  thrombi, 
which  usually  are  deposited  in  layers.  Sections  of  such  thrombi 
show  alternate  layers  of  white  and  red  thrombi.  The  most  extensive 
thrombus  formation  is  found  in  those  aneurysms  which  connect 


THE  PATHOLOGICAL  ANATOMY  OF  THE  HEART,  ETC.  8l 

with  the  artery  by  a  small  lumen  and  in  which  there  is  the  greatest 
opportunity  for  stagnation  of  the  blood.  The  senile  forms  of 
arterio-sclerosis  may  be  associated  with  diffuse  dilatation  of  the 
vessels,  but  rarely  lead  to  true  aneurysms,  and  the  same  is  true  of 
general  nonspecific  arterio-sclerosis.  Aneurysm  is  most  common 
at  an  age  prior  to  that  in  which  arterio-sclerosis  is  most  likely  to 
occur.  The  frequency  of  aneurysm  in  the  ascending  portion  and 
the  arch  of  the  aorta,  those  portions  most  affected  by  syphilitic 
arterio-sclerosis,  together  with  the  statistical  evidence  of  the 
association  of  aneurysm  of  the  aorta  with  syphilis  points  to  this 
disease  as  an  extremely  frequent  cause. 

Aneurysms  may  form  also  when  the  degeneration  of  the  wall  is 
due  to  causes  acting  from  without.  When  a  tuberculous  cavity  in 
the  lung  comes  in  contact  with  a  branch  of  the  pulmonary  artery 
and  the  tuberculous  necrosis  extends  into  the  wall,  an  aneurysmal 
dilatation  may  take  place  at  the  weakened  point  and  fill  the 
entire  cavity.  The  sudden  and  fatal  haemorrhages  which  take 
place  in  tuberculosis  usually  are  due  to  the  rupture  of  a  small 
aneurysm  of  a  pulmonary  vessel.  In  the  same  way  aneurysms  of 
the  aorta  may  be  due  to  infections  of  the  adventitia  which  extend 
into  and  weaken  the  media;  and  in  rare  cases  they  may  be  due  to 
infections  of  the  intima.  Aneurysms  may  be  formed  also  as  the 
result  of  trauma.  The  tissue  formed  in  repair  is  not  so  capable  of 
resistance  and  gives  way  to  the  blood  pressure. 

A  special  form  of  aneurysm  is  known  as  miliary  aneurysm  and 
occurs  more  frequently  in  the  arteries  of  the  brain  than  elsewhere. 
They  are  multiple  and  like  other  aneurysms  due  to  degeneration  of 
the  arterial  wall,  which,  in  the  arteries  within  the  brain  tissue,  is 
thin  and  slightly  resistant.  Haemorrhage  within  the  brain  fre- 
quently is  due  to  the  rupture  of  such  aneurysms*  Another  form  of 
aneurysm  is  the  dissecting  aneurysm.  This  is  due  to  an  incomplete 
rent  in  the  wall,  and  the  blood  current  then  forces  its  way  into  the 
tissue  separating  the  coats.  Such  rents  take  place  usually  in 
arteries  whose  walls  have  been  weakened  by  arterio-sclerotic 
processes.  The  blood  may  coagulate  in  the  tissue,  or  in  rarer  case 
communication  with  the  lumen  of  the  vessel  may  be  established  by 
another  fissure  lower  down.  In  this  way  a  definite  cavity  which 
gradually  becomes  covered  with  endothelium  may  be  formed 
around  the  artery  and  a  double  circulation  be  established.  Such 


82  PATHOLOGY 

dissecting  aneurysms  may  also  occur  in  arteries  of  small  size. 
Pathological  communication  may  be  formed  between  veins  and 
arteries  either  with  or  without  the  preceding  formation  of  an 
aneurysmal  sac. 

An  aneurysm  when  once  formed  continues  to  increase  by  expan- 
sion. All  tissues  gradually  give  way  before  the  constant  pressure 
and  the  hammering  of  the  blood  current.  An  aneurysm  given  off 
from  the  posterior  portion  of  the  aorta  may  produce  erosion  of  the 
vertebrae  where  it  comes  in  contact,  and  erosion  of  the  sternum  may 
be  produced  from  aneurysm  of  the  arch.  The  death  of  the  in- 
dividual with  aneurysm  frequently  is  due  to  rupture. 

EXPERIMENTS.  The  experiments  in  circulation  cover  the  simpler 
experiments  in  thrombosis  and  embolism  and  the  physiology  of 
certain  pericardial,  myocardial  and  endocardial  lesions,  (i)  Under 
anaesthesia,  aseptically  expose  the  jugular  vein  of  a  cat,  sear 
lightly  with  a  hot  platinum  needle,  and  after  three  minutes,  excise, 
fix,  imbed  and  section.  Platelet  thrombosis  occurs.  (2)  Under 
anaesthesia  and  aseptically,  mechanically  injure  the  jugular  vein 
of  a  cat  by  pinching  and  twisting  in  a  haemostatic  forceps.  The 
carotid  can  be  injured  or  tied  off  in  the  same  animal  and  at  autopsy 
twenty-four  hours  later,  the  thrombosis  in  both  vessels  studied. 
(3)  Under  anaesthesia,  aseptically  insert  into  the  aorta  of  a  dog, 
through  the  external  iliac  artery,  by  means  of  a  special  cannula 
a  number  of  tobacco  seeds.  Manually  compress  the  mesenteric 
arteries  at  the  time  of  injection  so  as  to  avoid  mesenteric  infarction. 
Autopsy  at  the  end  of  one  week  and  study  the  infarcts  in  kidney  and 
spleen,  both  grossly  and  histologically.  (4)  Inject  2  c.c.  olive  oil 
into  the  posterior  auricular  vein  of  a  rabbit.  Observe  the  symp- 
toms, and  after  death  perform  autopsy,  studying  especially  frozen 
sections  of  lung,  brain,  kidney  stained  with  Scharlach  R.,  for  the 
oil  (fat)  emboli.  (5)  Under  anaesthesia  connect  the  carotid  artery 
of  a  cat  with  the  mercury  manometer,  make  pneumograph  connec- 
tions and  inject  into  the  femoral  vein  30  c.c.  air  in  portions  of 
10  c.c.  Study  the  tracings  of  blood  pressure,  pulse  and  respira- 
tion. Autopsy,  clamping  off  the  great  vessels  and  open  the  heart 
under  water  to  show  the  air  in  the  right  side.  The  auricle  and 
ventricle  frequently  show  foamy  fibrin  thrombi  also.  (6)  Hydro- 
pericardium  may  be  produced  by  opening  the  thorax  of  a  dog  under 
ether  anaesthesia  and  artificial  respiration,  and  injecting  into  the 


THE  PATHOLOGICAL  ANATOMY  OF  THE  HEART,  ETC.     83 

pericardium  from  30  to  75  c.c.  olive  oil.  Connect  the  femoral 
artery  with  the  manometer  and  note  the  depression  of  cardiac 
action  shown  in  the  kymographic  tracings.  (7)  Aortic  stenosis. 
Under  ether  anaesthesia  and  artificial  respiration,  open  the  thorax 
of  a  dog  and  constrict  the  aorta  near  its  origin  by  means  of  a  heavy 
silk  ligature.  Note  the  effects  by  the  kymographic  registration 
of  heart  action  and  blood  pressure.  (8)  Aortic  regurgitation  may 
be  produced  in  the  same  animal  by  introducing  a  valve  hook 
through  the  carotid  artery  and  tearing  the  aortic  valve.  The 
effect  on  the  circulation  is  marked  by  a  notable  fall  in  pressure  and 
the  establishment  of  the  water  hammer  pulse.  All  the  valve 
lesions  are  to  be  studied  with  the  multiple  stethoscope.  (9)  Myo- 
cardial  degeneration.  Under  ether  anaesthesia  and  artificial  res- 
piration open  the  thorax  of  a  dog  and  inject  into  the  cardiac 
muscle,  in  numerous  places,  small  amounts  of  95  per  cent  alcohol. 
With  kymographic  registration  note  the  great  reserve  force  of  the 
heart  and  the  final  fall  in  pressure  and  arrhythmia  after  a  large 
part  of  the  muscle  has  been  incapacitated.  (10)  Arterio-sclerosis. 
Inject  into  the  posterior  auricular  vein  of  a  young  rabbit  three 
drops  adrenalin.  Inject  daily  for  one  week,  increasing  the  dose 
by  one  drop  each  day.  Autopsy  at  the  end  of  two  weeks  and  care- 
fully observe  the  aorta,  making  sections  of  the  vessel  and  of  the 
cardiac  muscle.  The  latter  frequently  shows  myocardial  degenera- 
tion, fibrous  myocarditis  and  hypertrophy. 


83  a 


83  b 


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83d 


83  e 


83  f 


83  g 


83h 


83  i 


83  j 


83  k 


83  1 


83m 


83  n 


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83  q 


83  r 


83  s 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION 

The  amount  of  work  accomplished  by  the  heart  is  determined  by 
the  amount  of  blood  it  projects  into  the  aorta  in  systole,  the  number 
of  contractions  in  a  given  time,  and  the  degree  of  arterial  pressure 
which  the  blood  overcomes  in  entering  the  aorta.  The  work  even 
under  normal  conditions  varies  constantly  and  widely  and  the 
heart  readily  adapts  its  activities  to  meet  new  conditions.  In- 
creased demands  for  work  are  met  by  increase  in  the  frequency  and 
force  of  contractions.  The  various  pathological  conditions  of  the 
heart  and  pericardium  affect  the  work  by  impeding  the  entry  of 
blood  into  the  heart,  its  passage  through  and  from  the  heart  and 
by  diminishing  its  power  of  contraction. 

Pathological  conditions  of  the  pericardium  interfere  with  the 
function  of  the  heart  in  two  ways,  (a)  Accumulation  of  fluid 
within  the  cavity  interferes  with  the  entry  of  blood  by  increasing 
the  pressure  around  the  heart.  The  effect  of  the  pressure  is  felt 
chiefly  on  the  large  vessels  with  relatively  thin  walls  which  enter 
the  heart,  and  also  on  the  auricles.  The  pressure  on  the  venous  side 
is  increased  and  the  blood  pressure  diminished  by  the  small  amount 
of  blood  which  passes  through  the  heart  and  into  the  aorta.  Much 
depends  upon  the  rapidity  with  which  the  fluid  collects,  for  the 
cavity  is  distensible  and  the  outer  wall  yields  under  pressure.  In 
dropsical  conditions  in  which  the  fluid  collects  very  slowly  very 
large  amounts  of  fluid  may  exert  but  little  pressure;  on  the  other 
hand,  a  small  amount  of  fluid  rapidly  formed,  for  example,  an  acute 
inflammatory  exudate,  produces  very  considerable  pressure.  The 
greatest  degree  of  pressure  will  be  produced  in  cases  of  rupture  of 
the  heart  or  of  the  great  arteries  within  the  pericardium,  in  which 
cases  the  pressure  within  the  pericardium  increases  so  rapidly  that 
a  small  haemorrhage  prevents  the  expansion  of  the  heart.  But  when 
the  opening  into  the  pericardial  sac  is  small,  very  oblique  or 
tortuous,  the  haemorrhage,  although  constant,  may  be  very  slight 
and  a  large  quantity  of  blood  may  collect  before  the  pressure  be- 
comes sufficient  to  stop  the  heart.  Tumors  of  the  mediastinum 

84 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     85 

by  the  pressure  which  they  exert  on  the  heart  or  great  vessels  may 
act  in  much  the  same  way  as  increased  pericardial  pressure.  Peri- 
cardial  pressure  has  a  further  interest  in  the  fact  that  the  circula- 
tory disturbances  produced  cannot  be  compensated  for  by  increased 
activity  of  the  heart. 

(6)  Other  pathological  conditions  of  the  pericardium  can  affect 
the  work  of  the  heart  by  interfering  with  its  contraction.  Simple 
obliteration  of  the  pericardial  cavity  due  to  adhesions  after  peri- 
carditis have  little  or  no  effect,  but  when,  as  is  often  seen  in  tuber- 
culous pericarditis,  the  heart  becomes  surrounded  by  dense  masses 
of  tissue  often  0.5  cm.  thick,  the  presence  of  such  an  unyielding 
inert  mass  offers  resistance  to  contraction.  The  condition  becomes 
worse  when  thick  pleuritic  adhesions  are  added  to  the  pericarditis. 
Under  such  conditions  extreme  hypertrophy  and  dilatation  of  the 
heart  results. 

The  various  pathological  changes  in  the  valves  produced  by  endo- 
carditis impede  the  passage  of  blood  through  and  from  the  heart. 
The  valves  become  incapable  of  closing  the  openings  which  they 
guard,  insufficiency,  through  shortening  brought  about  by  destruc- 
tion or  contraction  of  cicatricial  tissue,  through  adhesions  to  the 
cardiac  wall  and  through  contraction  of  the  chordae  tendineae. 
On  the  other  hand,  in  stenosis,  by  adhesions  between  the  valves  and 
by  calcification  the  openings  may  be  diminished  in  size.  In  the 
majority  of  cases  of  valvular  disease  varying  degrees  of  both 
stenosis  and  insufficiency  are  present.  The  normal  muscular  con- 
traction of  the  heart  is  essential  for  the  action  of  the  auriculo- 
ventricular  valves,  for  in  the  contraction  the  ring  of  insertion  is 
diminished  in  size.  Dilatation  of  the  heart  may  produce  a  relative 
insufficiency  of  the  valves  by  the  enlargement  of  the  orifices. 

The  simplest  of  these  conditions  is  seen  in  the  rare  cases  of  un- 
complicated stenosis  of  the  aortic  valves.  This  is  overcome  by 
hypertrophy  of  the  left  ventricle  which  enables  it,  by  the  increase 
in  the  force  of  contraction,  to  project  the  normal  amount  of  blood  in 
the  same  time  through  the  narrowed  orifice.  Much  more  common 
is  the  condition  in  which  the  orifice  is  not  only  narrowed,  but  the 
valve  incapable  of  accurate  closure.  The  ventricle  then  must  hold 
and  project  a  much  greater  amount  of  blood,  for  a  large  proportion 
of  the  blood  ejected  regurgitates  during  diastole,  from  the  aorta  back 
into  the  ventricle.  Not  only  this,  but  in  diastole  the  ventricle  is 


86  PATHOLOGY 

more  easily  filled  by  the  forceful  backward  flow  from  the  aorta  than 
from  the  auricle.  A  diastolic  intra ventricular  pressure  is  produced 
which  leads  to  increased  pressure  within  the  auricle  and  to  hyper- 
trophy. Stenosis  of  the  mitral  valve  is  a  more  complicated  condi- 
tion, for  the  increased  pressure  within  the  auricle  extends  into  the 
pulmonary  circulation  and  throws  more  work  on  the  right  side  of 
the  heart,  for  the  blood  must  be  forced  through  the  lungs  against 
pressure.  Hypertrophy  of  the  left  auricle  takes  place,  but  no  hyper- 
trophy of  the  left  ventricle  because  no  increased  work  is  thrown 
upon  the  latter.  When,  however,  there  also  is  insufficiency,  the 
left  ventricle  dilates  and  hypertrophies  as  well,  for  in  systole  the 
normal  amount  of  blood  must  be  projected  into  the  aorta  in  spite 
of  the  amount  which  regurgitates  into  the  auricle.  So  important 
is  the  contraction  of  the  heart  in  assisting  the  action  of  the  mitral 
valve  that  an  apparent  insufficiency  of  the  valve,  as  determined  by 
autopsy,  may  not  really  have  been  such  in  life. 

Valvular  disease  in  the  right  side  of  the  heart  is  much  less  fre- 
quent than  in  the  left.  In  the  rare  cases  of  stenosis  and  insufficiency 
of  the  pulmonary  valves  the  right  ventricle  hypertrophies.  Hyper- 
trophy of  the  right  side  of  the  heart,  however,  is  more  frequently 
the  result  of  high  pulmonary  pressure  brought  about  (a)  by  patho- 
logical conditions  in  the  lungs  which  diminish  the  sectional  area  of 
the  pulmonary  vessels,  or  (6)  by  increase  of  auricular  pressure  on 
the  left  side  of  the  heart.  Hypertrophy  of  the  right  ventricle 
depending  upon  impediments  in  the  pulmonary  circulation  from 
disease  of  the  lungs  varies  in  degree  according  to  the  disease.  It 
is  almost  invariably  present  in  emphysema  of  the  lungs  while  in 
advanced  destruction  of  lung  tissue  in  cases  of  tuberculosis  it  usually 
does  not  take  place.  This  is  due  to  the  fact  that  in  tuberculosis 
the  work  of  the  heart  is  reduced  by  the  invalid  life  of  the  patient, 
while  in  emphysema  there  may  be  but  little  impairment  of  the  usual 
activity,  and  the  work  of  the  heart  is  increased  not  only  by  the 
diminution  of  the  sectional  area  of  the  vessels,  but  in  addition  to 
this,  the  rapidity  of  the  stream  must  be  increased  in  order  that  the 
diminished  respiratory  surface  shall  suffice  for  oxygenation. 

Hypertrophy  of  the  heart  takes  place  much  more  easily  in  the 
young  than  in  older  persons,  and  slight  valvular  defects  in  the 
young  may  be  so  perfectly  compensated  that  an  efficient  circulation 
is  maintained.  In  most  cases  the  heart  which  has  compensated  for 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION      87 

an  injury,  however  perfect  the  compensation  may  appear,  is  not  as 
perfect  a  machine  as  the  normal  heart,  in  that  there  is  diminished 
reserve  force.  The  compensation  demands  increased  resistance 
to  dilatation  under  increased  fluid  pressure,  as  well  as  increased 
force  of  muscular  contraction.  The  power  of  the  dilated  heart  is 
weakened  owing  to  the  increase  of  the  surface  area  over  which  the 
pressure  must  be  raised.  Conditions  which  increase  the  work  of 
the  heart,  such  as  severe  exercise,  psychic  disturbances,  pregnancy, 
or  those  producing  degrees  of  degeneration  of  the  muscle  fibres  as 
infections  and  fever,  which  could  easily  be  met  by  the  reserve  force 
of  the  heart,  may  quickly  break  down  the  compensation  in  both 
pressure,  resistance  and  force  contraction.  The  dilatation  which 
then  occurs  adds  to  the  valvular  imperfections  by  the  dilatation 
of  the  orifices.  Probably  hi  the  hypertrophied  heart  there  also  is 
less  in  the  power  of  resistance  of  the  hypertrophied  muscles  fibres 
to  pathological  conditions  acting  upon  them  and  also  a  loss  in  the 
reserve  nutritive  capacity  of  the  coronary  circulation.  The  diam- 
eter of  the  coronary  arteries  does  not  increase  pari  passu  with  the 
increased  size  of  the  heart  and  pathological  conditions  of  the  myo- 
cardium are  much  more  common  than  in  normal  hearts. 

All  the  pathological  conditions  of  the  myocardium  act  by  inter- 
fering with  both  the  resisting  and  contractile  power  of  the  heart. 
Apart  from  the  acute  degenerations  of  the  muscle  fibres  due  to  the 
action  of  toxic  substances  engendered  in  the  course  of  infections, 
the  most  serious  lesions  of  the  myocardium  are  in  connection  with 
disease  of  the  coronary  arteries.  Complete  obliteration  of  one 
coronary  artery  or  even  a  considerable  branch,  if  produced  suddenly, 
is  usually  fatal.  Closure  of  a  smaller  branch  may  be  followed  by 
necrosis  and  infarction  of  the  area  which  it  supplies.  Chronic 
degeneration  of  the  myocardium,  followed  by  formation  of  connec- 
tive tissue  (fibrous  myocarditis),  frequently  is  associated  with 
arterio-sderotic  changes  of  the  vessels.  Sudden  death  may  result 
from  narrowing  of  the  calibre  without  occlusion.  In  such  cases 
apparently,  the  blood  supply  may  just  suffice  for  the  mean  activity 
of  the  cardiac  muscle  and  any  sudden  demand  for  increased  blood 
supply  cannot  be  met.  The  degeneration  of  the  myocardium, 
involving  the  auriculo-ventricular  bundle  of  His,  brings  about  a 
disturbance  of  the  associated  contraction  of  auricle  and  ventricle. 
The  action  of  the  heart,  whether  the  neurogenic  or  the  myogenic 


88  PATHOLOGY   j 

theory  of  contractility  is  accepted,  is  influenced  by  nervous  supply, 
and  disease  of  the  nerves  may  affect  it,  producing  abnormal  fre- 
quency of  contraction  (tachycardia),  or  abnormal  slowness  (brady- 
cardia),  or  various  grades  of  arrhythmia. 

When  the  heart,  either  temporarily  or  continuously,  is  insufficient 
that  is,  is  incapable  of  doing  the  normal  amount  of  work,  there  occurs 
a  fall  in  the  arterial  pressure  due  to  the  diminished  output  of  blood 
into  the  aorta  and  an  accumulation  of  blood  on  the  venous  side 
producing  increased  venous  pressure.  All  the  disturbances  which 
arise  in  consequence  of  insufficiency  of  the  cardiac  force  lead  to  a 
slowing  of  the  blood  current,  which  is  of  more  importance  for  the 
function  of  the  organs  than  the  diminution  of  the  blood  pressure. 
A  diminution  of  the  blood  pressure  primarily  brought  about  by  a 
diminution  in  the  amount  of  blood  projected  by  the  systole  into 
the  aorta  is  compensated  for  by  contraction  of  the  small  arteries 
which  brings  the  diminished  blood  amount  into  a  diminished 
vascular  territory.  The  normal  metabolism  of  the  tissues  depends 
not  only  upon  the  proper  quality  of  the  blood,  but  on  the  amount 
which,  in  a  given  time,  passes  through  the  vessels.  The  activity 
of  the  lymphatic  circulation  is  closely  dependent  upon  that  of  the 
blood  and  increase  of  venous  pressure  is  followed  by  increase  of 
pressure  in  the  lymphatics.  The  slowness  of  the  circulation  in 
the  lungs  brings  about  the  respiratory  distress,  the  cardiac  dysp- 
ncria;  the  diminished  oxydation  of  the  blood  gives  a  blue  color  to 
the  skin  and  mucous  membranes,  cyanosis.  With  the  continued 
cardiac  weakness  and  the  venous  congestion,  gravity  operates  more 
readily  and,  as  a  result,  the  blood  accumulates  and  the  circulation 
becomes  least  active  in  the  most  dependent  parts.  With  the  con- 
sequer  t  diminution  in  metabolism  the  resisting  power  of  the  tissues 
is  diminished  and  infections  easily  occur.  The  relation  of  infections 
to  passive  congestion  is  complicated.  In  passive  congestion  of  the 
lungs  the  resistance  of  the  tissue  to  infection  with  the  tubercle 
bacillus  is  increased  and  an  actual  infection  may  take  a  more 
favorable  course.  The  artificial  production  of  passive  congestion 
acting  by  filling  the  tissue  with  bactericidal  fluids  may  favorably 
influence  various  local  infections.  Regeneration  of  tissue  does  not 
take  place  so  readily,  and  the  healing  wounds  and  inflammatory 
conditions  generally  do  not  pursue  a  favorable  course.  Nutrition 
is  impaired  not  only  by  the  character  of  the  circulation  in  the  tissues 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION      89 

but  also  by  the  interference  with  digestion  and  absorption  from  the 
intestinal  canal.  A  vicious  circle  is  established  in  which  a  condition 
resulting  from  an  imperfect  function  tends  to  increase  the  preceding 
functional  imperfection.  In  all  these  cases  there  can  be  compensa- 
tion brought  about  by  diminishing  the  demands  made  upon  the 
heart  by  bodily  activity  until  life  is  possible  only  in  bed  and  finally 
even  so  much  activity  as  is  involved  in  existence  becomes  impossible. 

In  chronic  passive  congestion  two  changes  are  almost  invariably 
found  in  all  tissues.  There  is  diapedesis  of  red  blood  corpuscles 
from  the  dilated  capillaries  and  increased  formation  of  the  inter- 
stitial tissue  of  organs,  with  associated  formation  of  elastic 
tissue.  It  is  uncertain  whether  such  a  growth  of  tissue  is  due 
primarily  to  the  passive  congestion  or  whether  it  is  secondary  to 
pathological  conditions  of  the  parenchyma.  Passive  congestion 
produces  certain  changes  in  the  organs  of  the  body  more  or  less 
characteristic  of  each.  Passive  congestion  may  be  brought  about 
in  organs  also,  by  local  obstruction  to  the  venous  outflow.  Occlu- 
sion of  single  veins  may  produce  little  or  no  result,  owing  to  the 
number  of  collaterals.  Pathological  conditions  in  the  liver  pro- 
ducing obstruction  in  the  portal  circulation  lead  to  passive  conges- 
tion in  the  entire  portal  territory. 

PASSIVE  CONGESTION  OF  THE  LUNGS.  In  this  the  lungs  do  not 
collapse  so  completely  on  opening  the  chest,  and  are  heavier,  more 
moist  and  more  resistant  than  normal.  The  color  is  dark  red, 
which,  in  more  chronic  cases,  passes  into  a  brick  red  (brown 
induration).  The  greater  consistency  of  the  lung  is  due,  in  great 
part,  to  the  greatly  dilated  capillaries  which  project  as  loops  into 
the  air  spaces.  The  alveolar  epithelium  is,  in  part,  desquamated. 
There  is,  not  infrequently,  fluid  in  the  alveoli  and  also  red  corpuscles 
which  pass  in  by  diapedesis.  These  corpuscles,  in  part,  pass  away 
by  the  lymph  streams,  in  part  they  are  taken  up  by  the  phagocytic 
alveolar  epithelium  and  converted  into  brown  iron-containing 
haemosiderin.  Not  infrequently  the  pigment  forms  around  small 
particles  of  carbon  which  the  cells  also  have  taken  up.  The  con- 
sistency of  the  tissue  also  is  added  to  by  an  increase  in  the  inter- 
stitial tissue. 

PASSIVE  CONGESTION  OF  THE  LIVER.  In  recent  cases  the  liver  is 
enlarged,  the  capsule  tense,  the  whole  surface  and  section  of  the 
organ  a  dark  red  in  which  the  central  veins  stand  out  as  dark  points. 


90  PATHOLOGY 

When  the  congestion  has  lasted  longer  the  dark  areas  around  the 
central  veins  increase  in  extent  and  contrast  sharply  with  a  pale  fat- 
containing  periphery.  This  mottling  of  dark  and  light  areas  has 
given  rise  to  the  term  "nutmeg  liver,"  the  appearance  somewhat 
resembling  that  seen  in  the  smooth  section  of  a  nutmeg.  On 
microscopical  examination  there  are  three  distinct  conditions.  In 
the  first  there  is  marked  dilatation  of  the  central  veins  and  dilata- 
tion of  the  capillaries  around  these,  extending  a  varying  distance 
towards  the  periphery  of  the  lobule.  The  liver  cells  in  the  area 
of  dilatation  are  preserved  but  atrophied.  In  the  second,  in  which 
the  nutmeg  appearance  is  very  marked,  the  liver  cells  about  the 
centres  of  the  lobules  have  almost  or  completely  disappeared, 
leaving  areas  which  are  converted  into  blood  lakes.  In  this  tissue 
the  remains  of  capillaries  can  be  found  and,  occasionally,  atrophied 
and  necrotic  liver  cells.  In  the  third,  there  is  a  true  haemorrhage 
into  the  tissue,  the  blood  being  both  in  the  capillaries  between  the 
cells  and  in  the  intervening  parenchyma.  In  certain  cases  the 
capillaries  seem  to  be  collapsed  and  the  slow  circulation  takes  place 
chiefly  through  the  intercapillary  areas.  In  such  a  condition  it  is 
not  improbable  that  there  may  have  been  a  central  necrosis  of  the 
liver  in  association  with  passive  congestion.  The  necrosis  in  cases 
of  endocarditis  may  have  been  produced  at  the  time  and  the  regener- 
ation of  the  liver  tissue  has  been  inhibited  by  the  imperfect  circu- 
lation. It  is  also  not  improbable  that  the  liver  cells  may  have 
become  necrotic,  owing  to  imperfect  nutrition.  In  the  most 
advanced  form,  cardiac  cirrhosis,  there  is  a  considerable  formation 
of  connective  tissue  in  the  centres  of  the  lobules,  associated  with 
the  atrophy.  In  these  cases  also  there  may  be  very  marked  forma- 
tion of  elastic  tissue.  There  is  little  or  no  formation  of  blood 
pigment. 

PASSIVE  CONGESTION  OF  THE  SPLEEN.  The  spleen  is  enlarged,  of 
firm  consistency,  and,  on  section,  of  a  dark  red  color.  Microscopi- 
cally, some  haemosiderin  pigment  usually  is  present  in  large  phago- 
cytic  cells  and  in  the  fibrous  trabeculae;  the  walls  of  the  veins  and 
the  reticulum  of  the  pulp  are  thickened.  A  greater  degree  of  con- 
gestion usually  is  present  when  the  obstruction  is  in  the  portal 
vein  than  when  it  is  due  to  cardiac  disease. 

PASSIVE  CONGESTION  OF  THE  KIDNEYS.  These  are  large,  firm 
and  dark  red.  The  congestion  is  more  marked  in  the  pyramids 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION      91 

which  are  sharply  separated  by  color  from  the  cortex,  the  venae 
rectae  standing  out  as  dark  red  lines.  In  the  cortex  the  glomeruli 
are  visible  as  red  points.  When  the  congestion  is  long  continued 
there  is  a  general  increase  of  the  fibrous  tissue,  more  marked  around 
the  vessels  and  foci  of  glomeruli  and  tubular  atrophy.  Not  in- 
frequently small  haemorrhages  are  found  between  the  tubules,  and 
red  corpuscles  find  their  way  into  the  lumina.  Hyalin  casts  in 
small  numbers  always  are  present  and  on  boiling  the  kidney  or 
fixing  thin  sections  in  coagulating  fluids,  a  granular  albuminous 
precipitate  often  is  found  in  the  capsular  spaces. 

PASSIVE  CONGESTION  or  THE  BRAIN.  The  changes  are  less 
evident  than  in  other  organs.  The  vessels  of  the  meninges  are 
prominent,  there  is  some  thickening,  the  tissue  contains  an  excess 
of  fluid  and  the  pia  arachnoid  is  more  easily  stripped  from  the 
convolutions  than  in  the  normal.  The  brain  is  somewhat  redder 
than  normal  and  the  vessels  of  the  white  matter  are  more  prominent 
on  section.  There  is  no  increase  of  the  neuroglia. 

PASSIVE  CONGESTION  OF  THE  INTESTINES.  The  vast  vascular 
area  of  the  portal  system  is  the  reservoir  in  which  the  blood  in 
venous  obstruction  chiefly  collects.  The  mucous  membrane  of  the 
intestines  is  thickened  and  dark  red.  The  surface  pile  formed  by 
the  villi  is  more  prominent.  When  the  obstruction  is  central  and 
the  lymphatic  pressure  is  increased  due  to  the  increased  pressure  in 
the  superior  cava,  not  infrequently  the  intestinal  lymphatics  are 
dilated  and  small  white  areas  filled  with  chyle  and  representing 
varicosities  are  found  in  the  mucous  membrane.  Although  the 
haemorrhage  by  diapedesis  is  considerable,  there  is  no  pigment  form- 
ation in  the  tissue,  the  red  corpuscles  being  quickly  carried  into  the 
lymphatics  and  into  the  mesenteric  lymph  nodes  which  in  extreme 
cases  of  congestion  may  be  reddened  by  the  blood  in  the  sinuses. 

The  effect  of  arterio-sclerosis  on  the  circulation  is  one  of  the  most 
perplexing  questions  in  pathology.  From  a  purely  physical  aspect 
the  arterial  tubes  may  be  irregular,  dilated  and  lengthened,  render- 
ing their  course  more  tortuous,  and  to  a  varying  degree  the  inner 
surface  is  less  smooth  than  normal.  In  certain  cases,  these  purely 
physical  alterations,  of  which  the  aneurysm  is  the  most  marked 
type,  appear  alone  or  are  the  most  prominent,  and  they  appear  to 
produce  little  effect.  The  opposition  to  the  current  is  easily  over- 
come by  a  slight  increase  in  the  cardiac  work  without  hypertrophy. 


92  PATHOLOGY 

When  the  arterial  disease  is  more  general  and  the  small  arteries  of 
the  organs  are  diseased  and  converted  into  rigid  conducting  tubes, 
the  influence  of  the  vaso-motor  nerves  removed  or  diminished  by  the 
greater  or  less  destruction  of  the  media,  the  effect  on  the  circu- 
lation is  more  serious.  For  one  thing  there  is  interference  with 
the  normal  distribution  of  blood,  and  the  reciprocal  relation  of 
vascular  territories.  Nor  can  there  be  maintained  the  perfect  rela- 
tion between  blood  supply  and  function.  It  is  in  these  cases  that 
high  arterial  pressure  and  heart  hypertrophy  are  found.  When  the 
arterial  disease  is  most  marked  in  the  arteries  controlled  by  the 
splanchnic  nerves,  inhibiting  the  influence  of  these  vessels  in  regu- 
lating the  circulation,  the  effect  on  the  circulation  is  most  marked. 
A  difficulty  is  found  in  separating  from  the  influence  of  arterial 
disease,  the  influence  of  the  almost  constant  accompaniment  of 
disease  of  the  kidneys.  Independently  of  arterio-sclerosis  chronic 
renal  disease,  producing  destruction  of  tissue  and  loss  of  function 
leads  to  the  presence  in  the  blood  of  substances  producing  increase 
in  blood  pressure;  the  increased  blood  pressure  in  the  arteries, 
already  less  resistant,  increases  the  arterio-sclerosis;  heart  hyper- 
trophy of  the  left  ventricle  results  owing  to  increased  work  thrown 
upon  it  to  overcome  the  arterial  pressure;  not  infrequently  the  same 
sclerotic  changes  of  the  arteries  affect  the  aortic  and  mitral  valves 
interfering  with  their  function;  to  the  heart  hypertrophy,  dilata- 
tion is  added,  the  disease  of  the  coronary  vessels  producing  lesions 
of  the  myocardium  which  renders  the  walls  less  resistant;  the 
auriculo-ventricular  valves  first  on  the  left,  then  on  the  right  side 
become  relatively  insufficient  and  general  passive  congestion  follows, 
with  the  evils  attendant  upon  it.  There  is  a  vicous  circle  widening 
with  ever  increasing  rapidity. 

I-LEMORRHAGE  is  the  passage  of  blood  from  the  vessels.  Haemor- 
rhages into  the  tissues  have  received  various  names,  as  petechia 
for  fine  punctiform  haemorrhages,  ecchymoses  for  larger  macular 
areas  of  haemorrhage,  and  hamatoma  when  the  mass  of  blood  in  the 
tissue  has  a  tumor-like  form.  Haemorrhage  by  rhexis  takes  place 
when  there  is  an  evident  rupture  in  the  vessel;  by  diapedesis  when 
no  rupture  is  apparent.  Rupture  in  vessels  may  result  from  wounds, 
from  over  distension,  or  from  destructive  processes,  such  as  ulcers  or 
necrosis,  extending  from  without  into  the  vessel.  Haemorrhage  by 
diapedesis  takes  place  from  the  capillaries  and  small  veins  and  is 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION      93 

found  in  a  great  number  of  pathological  conditions.  In  practically 
every  form  of  inflammation  some  red  corpuscles  are  found  in  the 
exudate.  In  many  cases  it  is  by  no  means  certain  that  the  corpus- 
cles pass  through  an  intact  wall;  in  extreme  dilatation  of  capillaries 
and  small  veins  small  fissures  may  be  formed  by  the  separation  of 
cells.  The  small  punctiform  haemorrhages  of  the  serous  surfaces, 
particularly  of  the  epicardium,  which  so  frequently  are  found  in 
death  from  infectious  diseases,  have  been  attributed  to  the  action 
of  a  toxin,  producing  necrosis,  or  to  solution  of  the  endothelial  cells. 
Necrosis  of  tissue  usually  is  associated  with  haemorrhage,  the  cor- 
puscles seeming  to  pass  with  great  ease  through  the  walls  of  the 
capillaries  of  the  necrotic  territory,  as  is  seen  in  the  infarction. 
Any  congestion  of  the  blood  in  a  capillary  territory  usually  is 
accompanied  by  diapedesis  of  red  corpuscles ;  this  is  one  of  the  most 
common  conditions  in  chronic  passive  congestion. 

In  certain  general  and  ill-understood  conditions,  as  in  scurvy 
and  in  purpura,  these  small  haemorrhages  in  the  tissue  form  a 
prominent  feature  of  the  disease.  The  haemorrhages  which  so 
frequently  accompany  jaundice  are  due  probably  to  the  toxic  action 
of  the  bile  salts  on  the  endothelial  cells.  Recently  the  haemorrhagic 
diseases  have  been  the  subject  of  intensive  experimental  and  clinical 
investigation  and,  as  a  result,  it  seems  clear  that  the  clotting  power 
of  the  blood  is  greatly  diminished  in  their  course.  The  clotting 
power  depends  on  (a)  the  balance  between  prothrombin  and  anti- 
thrombin;  (b)  a  sufficient  amount  of  calcium  salts,  and  (c)  a  suffi- 
cient amount  of  fibrinogen.  Excesses  of  antithrombin,  insufficient 
prothrombin  and  insufficient  amounts  of  fibrinogen  have  been 
demonstrated  in  several  human  cases  and  in  animals,  the  subjects 
of  experimentally  produced  haemorrhagic  diseases.  Such  defects 
appear  to  have  an  important  bearing  on  these  diseases.  Variations 
in  the  organized  constituents  of  the  blood  also  may  be  important 
since  it  has  been  found  that  a  reduction  in  the  number  of  platelets 
frequently  accompanies  haemorrhagic  disease.  The  relation  of  such 
reduction  to  these  diseases  has  not  definitely  been  determined. 

(EDEMA  is  an  increase  in  the  amount  of  tissue  fluid.  When  this 
affects  the  entire  subcutaneous  tissue  the  condition  is  described  as 
anasarca,  milder  degrees  are  known  as  dropsy  and  when  the  fluid 
accumulates  in  the  serous  cavities,  various  names,  such  as  ascites 
(belly),  hydro  pericardium,  hydrothorax,  designate  the  cavity  in 


94  PATHOLOGY 

question.  The  formation  of  the  tissue  fluid,  under  normal  condi- 
tions, is  due  to  the  intracapillary  pressure  tending  to  filter  the  plasma 
through  the  capillary  walls;  diffusion  depending  upon  the  inequality 
in  chemical  composition  between  the  blood  plasma  and  the  fluid 
outside  the  capillaries;  osmotic  pressure  which  varies  with  the 
molecular  concentration;  secretion  by  the  endothelial  cells.  The 
variations  in  the  character  and  the  amount  of  fluid  in  different 
parts  of  the  body  have  led  to  the  assumption  that  in  different 
organs  there  is  a  variation  in  the  permeability  of  the  walls  of  the 
capillaries. 

(Edematous  tissues  are  paler  than  normal,  owing  to  the  relative 
diminution  in  the  amount  of  blood;  they  are  more  transparent;  on 
pressure  the  fluid  can  be  forced  out  leaving  a  pit  or  depression  and, 
on  section,  fluid  exudes  from  the  cut  surface. 

(Edema  from  obstruction.  With  no  increase  in  the  formation  of 
the  tissue  fluid  oedema  may  result  from  obstruction  to  the  outflow. 
The  number  of  lymphatic  vessels  is  so  great  and  the  anastomoses  so 
abundant  that  closure  of  single  vessels  has  little  or  no  effect.  Even 
the  thoracic  duct  may  be  occluded  without  the  production  of  oedema. 
The  most  marked  instance  is  the  chronic  oedema  of  the  legs  and 
scrotum  due  to  extensive  obstruction  of  lymphatics  by  Filaria 
Bancrofti.  (Edema  from  the  decrease  of  tissue  pressure,  as  by 
removal  of  atmospheric  pressure  from  a  part,  is  closely  related  to 
obstructive  oedema,  although  in  this  case  to  the  effect  of  obstruction 
must  be  added  increase  in  formation  due  to  passive  congestion. 

(Edema  from  passive  congestion;  cardiac  oedema.  The  oedema 
here  is  due  to  the  increased  venous  pressure  assisting  in  capillary 
filtration,  on  the  principal  that  increase  in  pressure  of  the  filtering 
fluid  increases  the  rapidity  of  filtration;  to  increased  permeability 
of  the  capillary  walls  due  to  their  distention  and  malnutrition; 
probably  there  is  also  increase  in  osmotic  pressure  due  to  the 
retention  in  the  tissue  of  products  of  cell  activity.  The  oedema 
appears  only  when  the  passive  congestion  has  been  of  long  duration 
and  varies  with  the  duration  and  the  intensity  of  congestion.  The 
oedema  appears  first  in  the  most  dependent  parts,  in  which  the  effect 
of  gravity  increases  the  congestion.  (Edema  also  appears  when 
the  venous  obstruction  affects  certain  areas  only  as  in  obstruction 
to  the  portal  circulation  produced  in  cirrhosis  of  liver,  ascites  being 
the  most  common  result. 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION      95 

RENAL  (EDEMA.  (Edema  is  one  of  the  most  common  conditions 
in  renal  disease.  It  does  not  coincide  in  presence  or  degree  with 
the  destruction  of  the  kidney  parenchyma.  It  is  especially  com- 
mon in  those  forms  of  renal  disease  in  which  lesions  of  the  glomeruli 
are  most  evident.  Various  theories  have  been  advanced  in  explana- 
tion of  such  oedema,  of  which  the  most  prominent  are  (i)  the 
retention  of  substances  in  the  tissue  which  increase  the  osmotic 
pressure  of  the  tissue  fluid,  (2)  the  presence  of  substances  in  the 
blood  which  increase  the  permeability  of  the  wall  of  the  vessel. 

A  CASE  OF  CHRONIC  AND  ACUTE  ENDOCARDITIS  WITH 
STREPTOCOCCUS  INFECTION 

Anatomical  Diagnosis.  Chronic  endocarditis  of  mitral  and  aortic 
valves;  Acute  endocarditis  of  mitral,  aortic  and  tricuspid  valves; 
Hypertrophy  and  dilatation  of  heart;  General  chronic  passive 
congestion;  General  anasarca;  Ascites;  Hydropericardium; 
Hydrothorax;  Infarction  of  lung;  Streptococcus  septicaemia; 
Focal  necrosis  of  liver. 

Female,  white,  age  five  years.  Body  well  developed  and  well  nour- 
ished. General  anasarca.  Face  cyanotic. 

Peritoneum  smooth.  The  cavity  contains  1800  c.c.  of  clear,  straw- 
colored  fluid.  Mesenteric  lymph  nodes  normal.  Diaphragm  on  left 
side  at  seventh  rib,  on  right  side  at  sixth  intercostal  space.  Each 
pleural  cavity  contains  a  large  amount  of  fluid  similar  to  that  in  the 
peritoneum. 

Pericardial  cavity  contains  300  c.c.  of  similar  fluid.  The  heart  weighs 
450  grams.  All  cavities  distended  and  filled  with  fresh  clot,  the  heart 
appearing  enormously  enlarged.  On  the  tricuspid  valve  are  fibrinous 
and  translucent  elevations  not  over  i  mm.  hi  diameter,  scattered  closely 
along  the  line  of  junction  of  the  valve  curtains.  The  columnae  carnae  of 
the  ventricle  are  prominent.  The  wall  is  6  mm.  thick.  The  pulmonary 
valves  are  normal.  The  left  auricle  is  much  dilated  and  hypertrophied. 
The  mitral  valve  presents  a  funnel-shaped  opening,  the  edges  of  the  valves 
irregular,  greatly  thickened  and  shortened.  This  condition  extends  to 
the  chordae  tendineae.  The  aortic  valves  are  thickened  and  shortened. 
Along  the  free  edge  of  both  mitral  and  aortic  valves  are  numerous 
minute  vegetations,  the  edges  not  over  2  mm.  hi  diameter,  appearing  as 
irregular  translucent  or  pink  excrescences  along  the  irregular  edges  of 
the  valves.  The  wall  of  the  left  ventricle  is  12  mm.  thick. 

Lungs.  Pleural  surface  smooth,  on  section  the  consistency  greatly 
increased,  the  tissue  of  a  brick  red  or  brown  color.  There  are  three 


96  PATHOLOGY 

areas,  two  in  the  right  and  one  in  the  left  lung,  wedge-shaped,  with  the 
base  on  pleura,  dark  red  in  color,  sharply  circumscribed,  a  solid  edge 
projecting  both  from  the  cut  surface  on  section  and  above  the  pleural 
surface.  The  largest  of  these  areas  is  3  cm.  in  diameter. 

Spleen  weighs  125  grams.  Deeply  congested.  Consistency  increased, 
pulp  dark  red,  trabeculae  prominent,  malpighian  bodies  not  visible. 

Liver,  weight  1200  grams.  Consistency  increased,  on  section  typical 
nutmeg  marking  appearing  as  small,  irregular  brown  or  red  areas  in  a 
field  of  yellow. 

Gastro-intestinal  tract  shows  injection  of  the  mucous  surface. 
Pancreas  normal. 

Kidneys  firm.  On  section  pyramids  deep  red  brown  in  color,  cortex 
paler.  Markings  distinct.  Glomeruli  appear  as  red  pin  point  specks. 
Pelvic  organs  normal,  aorta  normal.  Organs  of  the  head  not  examined. 
Microscopical  examination.  Sections  of  the  mitral  valve  show  great 
sclerotic  thickening  of  the  valve  with  polynuclear  leucocytes  and  lym- 
phocytes around  the  small  vessels  in  the  valve.  The  nodular  projections 
on  the  free  edge  are  composed  chiefly  of  masses  of  blood  plates  with  some 
fibrin  and  red  blood  corpuscles.  Immediately  beneath  this  and  in  the 
substance  of  the  valve  are  large  masses  of  polynuclear  leucocytes  and 
red  blood  corpuscles,  among  which  are  a  few  cocci  in  chains  and  not 
enclosed  in  cells.  Section  of  the  liver  show  the  capillaries  about  central 
vein  much  distended  and  the  liver  cells  atrophied.  This  is  sometimes 
symmetrically  concentric  about  the  central  vein,  but  is  often  irregular. 
The  liver  cells  in  the  centre  of  the  lobules  contain  considerable  golden 
yellow  pigment.  Small  areas  of  necrosis  are  irregularly  distributed  in 
the  lobule,  the  necrotic  cells  being  invaded  by  polynuclear  leucocytes. 
The  blood  cultures  made  at  autopsy  gave  the  streptococcus  pyogenes  in 
pure  culture. 

REMARKS.  The  condition  dates  from  the  primary  infection  of 
the  mitral  valves,  the  date  of  which  cannot  be  ascertained.  There 
was,  at  this  time,  destruction  of  tissue  of  both  valves  of  the  left 
heart,  but  particularly  the  mitral,  which,  with  the  thickening  and 
contraction,  rendered  them  insufficient.  There  does  not  seem  to 
have  been  stenosis.  The  heart  hypertrophy,  general  passive  con- 
gestion, anasarca  and  dropsy  followed.  The  vegetations  on  the 
valves  are  due  to  a  fresh  infection  of  the  valve  surface  by  the 
streptococcus.  This  organism  was  found  not  only  in  the  valvular 
lesion,  but  in  the  cultures  made  from  the  blood.  The  infarction  of 
the  lung  is  due  to  emboli  from  the  fresh  vegetations  on  the  tricuspid 
valve.  The  liver  shows  the  well-marked  lesions  of  chronic  passive 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     97 

congestion  and  in  addition  focal  necrosis.  Focal  necrosis  of  the 
liver  is  very  frequently  associated  with  streptococcus  infection. 
The  necroses  are  usually  much  more  symmetrically  placed  around 
the  central  vein,  but  they  may  be  irregular,  as  in  this  case.  The 
liver  necrosis  is  due  to  the  action  of  toxins. 


Anatomical  Diagnosis.  Chronic  mitral  endocarditis;  Acute  vege- 
tative mitral  tricuspid  and  pulmonary  endocarditis,  with  perfora- 
tion of  mitral  valve;  Hypertrophy  and  dilatation  of  heart; 
Eccymoses  of  epicardium;  (Edema  of  pia;  Old  hemorrhage  and 
cyst  of  softening  in  right  internal  capsule;  Chronic  passive  con- 
gestion of  lungs,  liver,  spleen  and  kidneys;  Infarction  of  lungs, 
spleen  and  kidney;  Chronic  fibrous  pleuritis;  Chronic  perihepat- 
itis;  Chronic  perisplenitis;  Anasarca  (hydrocele,  hydro  thorax, 
ascites);  Congestion  and  oedema  of  pharynx  and  larynx;  Strep- 
tococcus septicaemia;  arterio-sclerosis. 

White,  male,  age  twenty-four  years.  Body  well  developed  and  well 
nourished.  Chest  symmetrical.  Marked  bulging  of  precordial  region. 
Rigor  mortis  present.  Lividity  of  face  and  dependent  parts.  General 
oedema,  most  marked  in  scrotum  and  in  legs. 

Peritoneal  cavity.  Contains  100  c.c.  of  blood-stained  fluid.  Peri- 
toneum lusterless.  Splenic  flexure  of  colon,  firmly  adherent  to  hilum 
of  spleen  by  old  fibrous  bands.  Appendix  6  cm.,  free,  directed  inward 
and  downward.  Mesentery  lymph  nodes  slightly  enlarged.  Dia- 
phragm at  fifth  intercostal  space  on  left  side,  at  sixth  space  on  right  side. 
Bladder  markedly  distended. 

Pleural  cavities.  Left  side  contains  500  c.c.,  right  1000  c.c.  of  dark  red 
fluid.  Few  old  fibrous  adhesions  over  both  apices.  Inferior  surface 
of  lower  right  lobe  firmly  bound  to  diaphragm  by  old  fibrous  bands. 

Pericardial  cavity.  Contains  about  300  c.c.  of  clear,  straw-colored 
fluid. 

Heart.  Weight,  560  grams.  Heart  is  about  double  the  normal  size 
and  distended  with  clotted  blood.  The  coronary  veins  are  dilated. 
In  the  epicardium  are  innumerable  ecchymoses  discretely  sown.  On 
opening  the  heart,  the  mitral  valve  is  found  to  be  contracted,  thickened 
and  calcareous,  so  that  the  opening  measures  only  4  cm.  in  circumference. 
The  free  edge  of  the  valve  curtain  is,  moreover,  studded  with  minute 
wart-like,  soft  vegetations,  projecting  2  to  3  mm.  from  the  edge  of  the 
valve.  Between  the  base  and  free  edge  of  the  valve  is  an  aperture  0.5 


98  PATHOLOGY 

cm.  in  diameter,  the  edge  studded  with  minute  vegetations.  The  chordae 
tendineae  are  considerably  thickened  and  shortened.  The  aortic  valve 
appears  normal  save  for  a  single  vegetation  0.2  cm.  in  diameter  upon  the 
corpus  aurantium  of  the  middle  cusp.  The  left  auricle  is  greatly  dilated, 
the  wall  hypertrophied.  The  left  ventricle  is  1.25  cm.  in  thickness.  The 
muscle  is  firm  and  dark  red.  The  right  side  of  the  heart  is  much  hyper- 
trophied; the  right  ventricle  measuring  from  0.75  to  1.25  cm.  in  thick- 
ness. The  muscle  is  firm  and  shows  on  section  light-colored  areas. 
These  light-colored  areas  are  also  seen  on  the  endocardium  lining  the 
right  ventricle. 

The  tricuspid  valve  opening  is  enlarged,  13  cm.  in  circumference. 
The  free  edge  of  the  valve  curtain  shows  discrete  and  confluent  wart-like 
vegetations  similar  to  those  described  on  the  mitral  valve,  projecting 
2  to  4  mm.  from  the  edge  of  the  valve.  Their  transverse  diameter 
averages  3  mm.  The  pulmonary  valve  is  normal,  save  for  one  minute 
vegetation,  2  by  2  by  2  mm.,  situated  directly  between  two  of  the  cusps, 
a  little  back  from  the  free  edge  of  the  valve.  The  coronary  arteries  are 
normal. 

Lungs.  Voluminous,  heavy,  firm  and  resistant,  and  of  dark  reddish 
brown  color,  with  darker  and  firmer  areas  over  the  anterior  surface  of 
lower  lobes.  Upper  lobes  crepitate  and  pit  on  pressure.  Cut  section; 
anterior  surface,  upper  left,  shows  a  well-defined  dark  red,  firm,  elevated, 
dry,  wedge-shaped  area,  with  base  toward  surface  6  by  3.5  by  9  cm.  On 
anterior  surface,  right  lower  lobe,  are  two  similar  areas  2  by  1.5  by  2.5 
cm.  and  1.5  by  1.5  by  2  cm.  The  surrounding  tissue  on  pressure  emits 
dark  frothy  fluid.  Pulmonary  artery  and  its  larger  distributing  branches 
show  discrete  yellowish  areas  of  thickening.  Cruor  clot  in  pulmonary 
veins.  No  thrombus  or  embolus  detected. 

Spleen.  Weight,  140  grams.  Very  firm.  Capsule  thickened  over 
superior  surface  and  in  region  of  hilum.  Old  fibrous  adhesions  attach 
it  to  diaphragm  and  splenic  flexure  of  colon.  A  dark  brown  red  area 
1.5  cm.  in  diameter  on  anterior  surface  of  same  consistency  as  splenic 
substance.  On  superior  border,  yellowish-white,  wedge-shaped  area 
1.5  by  0.75  cm.  Malpighian  bodies  seen  as  small  translucent  dots  very 
thickly  sown.  Trabeculae  quite  prominent.  Pulp  does  not  readily 
come  away  on  scraping. 

Liver.  Weight,  1920  grams.  Large,  firm,  deep  red  organ,  edges 
rounded.  Anterior  surface,  right  lobe,  attached  to  diaphragm  by  long 
fibrous  cords.  Tip  of  left  lobe  firmly  bound  down  to  diaphragm  by  thick 
fibrous  band.  On  section  fairly  resistant  mottled  red  and  yellowish 
white  stellate  areas  (nutmeg  appearance).  Central  vessels  engorged, 
peripheral  vessels  collapsed. 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     99 

Kidneys.  Weight,  340  grams.  Right  organ  much  smaller  than  left. 
Capsule  thickened  and  strips  with  difficulty,  bringing  away  cortical 
substance.  Surface  pale  red,  lobulated  and  granular.  On  section  cuts 
with  difficulty.  Cortex  thinned  irregularly,  and  showing  faint  red 
parallel  lines  running  to  surface.  Glomeruli  visible  as  fine  sand-like 
particles.  Pyramids  dark  red  and  markedly  striated.  Right  kidney 
shows  several  grayish  white,  fine,  dry,  wedge-shaped  areas  with  the  base 
on  the  surface.  The  left  kidney  is  firm,  swollen  and  congested. 

Adrenals  normal. 

Gastro-intestinal  tract  apparently  normal. 

Pancreas  normal. 
,    Bladder  normal. 

Genital  organs  normal. 

Aorta.    Diffuse  yellowish  areas  of  thickening,  in  places  calcified. 

Organs  of  neck.  Tissue  about  pharynx,  larynx  and  trachea  show 
congestion  and  oedema. 

Head.  Brain,  weight,  1490  grams.  The  vessels  of  pia  injected.  The 
membrane  moist,  stripped  easily  from  convolutions.  Ventricles  contain 
about  5  c.c.  of  clear,  yellowish  fluid.  On  the  floor  of  right  lateral  ventricle 
extending  from  the  anterior  edge  of  the  eminence  formed  by  the  caudate 
nucleus  to  the  posterior  edge  of  the  eminence  of  the  optic  thalamus,  and 
external  to  both,  is  a  yellowish  elevated  area  3.5  cm.  long  by  0.75  cm.  in 
width.  In  the  substance  of  the  right  hemisphere  beneath  elevated  area 
described,  extending  antero-posteriorly  between  the  caudate  and  lenti- 
cular nuclei  is  a  cyst  flattened  horizontally,  4  cm.  long,  i  cm.  wide  and 
0.5  cm.  high.  This  cyst  is  divided  transversely  into  four  chambers  by 
thin  fibrous  partitions,  and  filled  with  soft,  brownish  debris  containing 
bright  yellow  masses. 

Middle  ears  normal. 

Cultures  from  blood  and  organs  gave  streptococci. 

REMARKS.  A  case  of  much  interest  in  the  interrelation  of 
lesions.  The  pathological  condition  began  with  an  acute  en- 
docarditis of  the  mitral  valve.  The  primary  disease  may  have 
been  of  a  severe  character  or,  as  often  happens,  there  may  have 
been  a  number  of  attacks,  the  result  being  thickening,  adhesion 
and  contraction  of  the  valve  producing  mitral  stenosis  and  the 
changes  of  the  heart  dependent  upon  this.  In  the  terminal  acute 
attack  the  valves  of  the  right  side  of  the  heart  were  also  affected 
and  there  was  further  extension  of  the  disease  of  the  mitral  valve 
producing  a  perforating  ulcer  of  the  valve.  In  consequence  of 
dilatation  of  the  right  ventricle,  the  tricuspid  valve  became  rela- 


ioo  PATHOLOGY 

lively  insufficient  producing  the  marked  passive  congestion  and 
cardiac  oedema.  Notice  that  the  oedema  is  most  marked  over  the 
lower  extremities  and  scrotum,  and  in  the  serous  cavities  the 
accumulated  fluid  has  a  red  tinge  due  to  admixture  of  blood.  The 
chronic  passive  congestion  in  the  lungs  is  marked  and  has  produced 
oedema  and  haemorrhage  into  the  alveoli.  There  are  a  number  of 
fresh  infarctions  due  to  emboli  from  the  vegetations  on  the  cardiac 
valves.  The  cyst  in  the  brain  is  the  result  of  embolus  and  infarc- 
tion. In  this  there  is  necrosis  and  haemorrhage,  which  may  have 
been  greater  in  amount  than  is  represented  by  the  size  of  the  cyst. 
The  clot  contracts  and  the  serum  is  absorbed.  Section  of  the  area 
would  have  shown  at  this  stage  a  slight  amount  of  fibrin  and  num- 
bers of  large  phagocytic  cells  containing  blood  pigment  and  fat 
from  the  necrotic  brain  tissue.  The  cyst  is  surrounded  by  neu- 
roglia.  The  area  does  not  undergo  organization  and  contraction, 
as  it  does  in  other  tissues,  for  connective  tissue  forms  to  but  a 
slight  extent  in  the  brain  and  cicatricial  contraction  does  not  take 
place  owing  to  the  closed  cavity  of  the  skull. 

Of  further  interest  in  the  case  is  the  arterio-sclerosis  of  the  aorta 
and  pulmonary  artery,  in  consideration  of  the  age.  The  pulmonary 
arteries  are  but  rarely  affected  in  arterio-sclerosis  and  in  this  case 
the  condition  is  probably  related  to  injury  of  the  arterial  wall  by 
the  increased  blood  pressure.  Arterio-sclerosis  of  the  aorta  to  the 
extent  described  here  is  not  very  uncommon  at  this  age.  Notice  that 
the  kidneys  are  unequally  affected;  the  left,  save  for  the  passive 
congestion,  is  normal  while  the  right  contains  recent  infarcts  and 
in  addition  is  irregularly  atrophied  and  contracted,  a  condition 
probably  due  to  infarctions  which  were  formed  at  the  time  of  the 
primary  attack. 

A  CASE  OF   EXTREME   DILATATION  OF  THE    HEART  WITH 
CHRONIC  MITRAL  STENOSIS  AND  EMPHYSEMA  OF  LUNGS 

Anatomical  Diagnoses.  Old  endocarditis  of  the  mitral  valve  with 
stenosis  and  insufficiency;  Chronic  emphysema  of  the  lungs; 
Heart  hypertrophy  and  dilatation;  Subacute  and  chronic  glo- 
merular  nephropathy;  Chronic  perisplenitis  and  perihepatitis; 
Passive  congestion  of.  the  liver  with  cirrhosis;  Chronic  pan- 
creatitis; General  passive  congestion;  Ascites;  Hydrothorax 
and  hydropericardium;  General  anasarca. 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION   101 

White,  male,  67^  years  of  age;  occupation,  butcher.  First  seen  in 
January,  1899,  when  his  symptoms  were  dyspnoea  and  feeling  of  exhaus- 
tion after  exertion.  From  this  time  until  1901  he  was  more  or  less  of 
an  invalid.  All  symptoms  pointed  to  faulty  myocardial  compensation. 
During  the  spring  and  summer  of  1901  was  very  sick.  At  this  time,  on 
examination,  the  cardiac  area  much  increased.  The  hepatic  pulsation 
was  marked;  there  was  pulmonary  oedema,  ascites,  oedema  of  extremities 
and  to  some  extent  of  the  body.  All  dimensions  of  the  heart  were 
increased,  the  apex  beat  was  diffuse  and  four  inches  outside  of  the  nipple 
line.  Action  of  heart  irregular  and  tumultuous,  the  entire  thorax  being 
shaken  by  the  pulsations.  The  liver  dullness  extended  a  hand's  breadth 
below  the  costal  cartilage.  The  urine  contained  blood  and  a  large 
amount  of  albumin  with  granular  and  hyalin  casts.  On  March  3ist, 
1908,  seen  again.  The  dyspnoea  on  exertion  was  more  marked.  Heart 
area  appeared  more  than  twice  the  normal  size.  Heart  sound  loud  and 
heard  distinctly  in  left  axilla.  There  is  a  mitral  murmur.  Heart  apex 
2\  inches  below  and  \\  inches  to  left  of  nipple  line.  Hepatic  area 
greatly  increased,  nearly  on  level  with  umbilicus.  Marked  pulsation 
over  liver  and  whole  chest.  No  evidence  of  fluid  in  abdominal  cavity. 
Urine  showed  large  amount  of  albumen,  hyalin  and  granular  casts. 
Weight,  195  pounds. 

In  June,  1909,  weight  about  the  same.  There  was  general  oedema  and 
the  cardiac  symptoms  were  exaggerated.  Urine  rather  scanty.  On 
October  5th,  phlebitis  and  thrombosis  of  left  leg,  which  was  relieved  by 
elevation  of  leg  and  bandage.  On  January  8th,  1910,  four  quarts  of 
blood-tinged  fluid  were  removed  from  abdominal  cavity.  During 
January  and  February  he  was  tapped  four  times.  All  symptoms  became 
exaggerated  and  he  spent  most  of  the  time  in  bed.  Died  suddenly, 
March  5th,  1910. 

The  body,  5  feet,  10  inches  long,  weight  195  pounds.  Body  heat  still 
present,  no  rigor  mortis  (autopsy  5  hours  after  death).  The  face  dusky 
purple.  There  is  a  general  oedema  of  the  body  most  marked  in  lower 
extremities  and  in  scrotum  which  measures  40  c.c.  in  circumference. 
There  is  desquamation  of  epithelium  over  ankles  and  legs.  Moderate 
post  mortem  lividity.  The  abdomen  distended  rising  8  cm.  above  level 
of  sternum.  Subcutaneous  fat  in  moderate  amount,  the  tissue  cedem- 
atous. 

The  peritoneal  cavity  contains  (estimated)  about  4000  c.c.  of  clear, 
slightly  reddish  fluid.  The  lower  border  of  the  liver  in  middle  is  9  cm. 
below  the  sternum,  and  in  the  nipple  line  6  cm.  below  the  rib  border. 
The  peritoneal  surface  injected  and  cloudy.  Dense  adhesions  about 
spleen  and  liver.  There  is  a  large  amount  of  fat  in  the  mesentery.  All 


102  PATHOLOGY 

the  veins,  particularly  those  in  the  lesser  omentum,  are  greatly  dilated. 
The  mesenteric  lymph  nodes  are  somewhat  enlarged  and  cedematous. 
A  series  of  lymph  nodes  adjoining  the  splenic  vein  and  the  post  peritoneal 
lymph  nodes  are  enlarged  and  of  a  brilliant  red  color.  The  diaphragm 
at  the  lower  border  of  the  fifth  rib  on  right  side,  at  the  sixth  rib  on  left. 
The  lungs  free  from  adhesions.  In  each  pleural  cavity  a  considerable 
amount  of  clear,  straw-colored  fluid. 

The  pericardium  fills  the  entire  space  between  rib  margins,  only  about 
6  cm.  of  the  upper  portions  of  lungs  visible.  In  the  pericardial  cavity 
a  large  amount  of  clear,  slightly  yellowish  fluid.  No  adhesions. 

The  heart  enormously  enlarged,  surface  smooth.  Epicardial  fat  in 
fair  amount.  The  heart  measures  with  cavities  distended  21  cm.  in 
length,  16  cm.  wide  and  8  cm.  antero-posteriorly.  The  great  increase 
in  size  principally  on  right  side.  Weight  of  heart,  780  grams.  The 
circumference  of  right  auricle  5  cm.  above  the  tricuspid  valve  is  27  cm. 
The  circumference  of  tricuspid  valve  at  attachment  is  17  cm.,  length  of 
right  ventricle  17  cm.  The  distension  of  the  auricle  is  so  great  that 
spaces  i  cm.  wide  appear  between  the  musculi  pectinati,  the  auricle 
resembling  a  distended  bladder.  The  myocardium  is  normal  in  color, 
no  evidence  of  fibrous  myocarditis.  The  average  thickness  of  wall  of 
right  ventricle  is  4  mm.  The  left  auricle  is  enlarged,  the  endocardium 
thickened  and  opaque,  circumference  of  auricle  18  cm.  The  left  ven- 
tricle is  hypertrophied  and  somewhat  dilated.  The  mitral  valve, 
particularly  the  aortic  segment,  is  contracted  and  in  part  calcified. 
The  chordae  tendineae  are  thickened  and  shortened.  The  edges  of  the 
valves  adherent.  The  circumference  of  mitral  opening  5.5  cm.  Both 
coronary  arteries  soft  and  free  from  clots.  The  right  greatly  di- 
lated, the  circumference  before  branching  1.4  cm.  The  left  slightly 
dilated. 

Arteries.  The  arteries  throughout  the  body  generally  in  good  con- 
dition. No  calcification  in  large  or  medium  arteries.  In  the  aorta, 
particularly  in  thoracic  and  abdominal  portions,  a  number  of  elevated 
plaques  some  of  which  show  slight  calcification. 

Lungs.  Pale,  air  containing  throughout,  no  oedema.  Mucous  mem- 
brane of  bronchi  pale. 

Spleen,  weight  330  grams.  Capsule  thickened,  areas  of  pale,  dense 
cartilaginous-like  tissue  in  capsule.  On  section  consistency  increased, 
coarsely  trabeculated,  hypersemic,  follicles  not  visible,  splenic  vein 
greatly  dilated. 

The  liver  enlarged,  weight  2050  grams.  Numerous  adhesions,  capsule 
thickened,  surface  finely  irregular  with  here  and  there  deeper  depres- 
sions. Along  the  anterior  border  of  the  liver  there  is  a  fine  granulation 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION   103 

of  the  surface,  the  granules  distinct  giving  the  appearance  of  grains  of 
fine  sand.  Color,  dark  brown  with  paler  foci.  On  section,  consistency 
increased,  the  lobulation  indistinct,  with  alternating  dark  and  pale 
areas.  The  vena  cava  at  liver  greatly  dilated,  its  walls  thickened, 
circumference  n  cm.  The  hepatic  veins  all  dilated,  their  walls  thick- 
ened. The  portal  vein  somewhat  dilated.  Gall  bladder  small,  the 
ducts  free. 

Gastro-intestinal  tract.  The  veins  of  the  cesophageal  plexus  dis- 
tended. The  mucous  membrane  of  stomach  and  intestines  is  injected 
Otherwise  normal. 

Adrenal  glands  normal. 

Pancreas.  Firm,  consistency  increased.  In  pancreatic  fat  there  are 
numerous  small  calcified  foci. 

The  kidneys  weigh  340  grams.  Of  the  same  size  and  general  ap- 
pearance. On  the  surface  of  the  right  kidney  several  deep  cicatrices. 
The  capsules  somewhat  adherent.  The  cortex  rather  pale,  markings 
obscure.  Pyramids  deeply  injected.  The  pelvic  fat  increased  in 
amount. 

Genitalia  and  bladder  normal. 

Microscopical  Examination.  Kidneys  show  focal  and  slight  diffuse 
increase  in  the  connective  tissue  of  cortex.  The  convoluted  tubules  are 
somewhat  dilated,  the  epithelium  small.  In  the  capsular  spaces  of 
glomeruli,  which  are  distended,  there  is  granular  coagulum.  The  walls 
of  the  capillaries  of  the  glomeruli  are  universally  thickened,  in  places 
the  lumina  are  closed  by  endothelial  cells,  poly  nuclear  cells  and  cellular 
detritis.  The  capsular  epithelium  of  the  tufts  is  swollen  and  the  cells 
increased  in  number.  Ip  several  places  the  glomerulus  opposite  the 
entering  vessels  has  become  attached  to  the  capsule  with  vascular 
connection  between  the  capsular  and  the  glomerular  vessels.  In  the 
larger  arteries  of  the  kidney  there  is  well-marked  arterio-sclerosis,  but 
is  not  evident  in  the  glomerular  arteries.  The  blood  vessels  are  generally 
injected,  particularly  those  of  the  pyramids.  No  distinct  points  of 
hemorrhage  are  found.  The  glomeruli  contain  a  small  amount  of  blood. 
A  few  red  corpuscles  are  found  in  the  tubules. 

The  pancreas  shows  a  very  considerable  formation  of  connective  tissue 
about  the  ducts  forming  a  definite  network  extending  throughout  the 
organ.  In  addition  there  is  a  diffuse  formation  of  connective  tissue  with 
atrophy  of  the  parenchyma  extending  into  the  acini.  All  the  Islands  of 
Langerhans  are  well  preserved.  The  bloodvessels  are  injected.  The 
arteries  show  slight  degrees  of  arterio-sclerosis. 

In  the  lymph  nodes  adjoining  the  mesentery  the  sinuses  are  distended 
with  blood.  The  lymphoid  tissue  is  normal.  All  the  blood  vessels  of 


104  PATHOLOGY 

the  node  are  strongly  injected.  The  afferent  lymphatics  are  greatly 
dilated  and  contain  granular  detritis  and  blood. 

Sections  of  the  lung  show  great  dilatation  of  all  of  the  pulmonary  veins 
with  a  high  degree  of  sclerosis  of  their  walls.  The  lung  is  emphysem- 
atous.  The  alveolar  walls  in  places  are  slightly  thickened  and  congested. 
The  alveoli  are  free  from  exudation,  but  contain  a  few  large  cells  con- 
taining blood  pigment. 

The  section  of  myocardium  of  the  right  ventricle  shows  well-marked 
congestion  and  general  increase  in  the  connective  tissue  and  oedema. 
All  of  the  fibres  are,  to  a  great  extent,  separated  from  one  another. 
Some  of  the  fibres  are  considerably  enlarged,  but  they  are  in  general 
well  preserved. 

REMARKS.  The  case  presents  many  features  of  interest.  The 
history  is  that  of  a  chronic  disease  of  the  heart  with  valvular  in- 
competence. The  condition  probably  began  with  an  acute  endo- 
carditis of  the  mitral  valve,  producing  a  stenosis  and  insufficiency, 
which  was  followed  by  hypertrophy  of  the  right  heart  and  dilata- 
tion. The  work  thrown  on  the  right  heart  was  greatly  added  to  by 
the  chronic  emphysema  of  the  lungs.  The  man  was  a  butcher  by 
occupation,  this  entailing  hard  work  at  intervals.  It  is  not  im- 
possible that  there  was  a  considerable  degree  of  dilatation  of  the 
heart  in  the  beginning,  associated  with  the  mitral  endocarditis  and 
that  it  increased  gradually  to  the  enormous  degree  described.  The 
dilatation  of  the  right  heart  is  extreme  and  the  tricuspid  valve  was 
functionless.  The  hypertrophy,  though  considerable  as  shown  by 
the  weight,  is  inconspicuous  compared  with  the  dilatation.  There 
was  also  some  degree  of  chronic  nephropathy  which  by  the  increase 
in  blood  pressure  incident  to  this  added  to  the  cardiac  work  and 
this  was  materially  added  to  by  the  subacute  glomerular  nephro- 
pathy, which  probably  dates  from  an  acute  erysipelas  which  he  is 
said  to  have  had  in  the  summer  preceding  death.  The  cicatrices 
noted  in  one  kidney  can  be  traced  to  infarctions  due  to  emboli  from 
the  mitral  valve. 

The  impediment  to  the  passage  of  blood  through  the  heart  led  to 
chronic  congestion  in  the  systemic  veins.  The  condition  in  the 
liver  shows  atrophy,  destruction  of  tissue  and  following  this  an 
increase  in  the  connective  tissue  in  both  areas  in  the  lobule.  The 
systemic  veins  in  all  the  organs  show  the  same  condition  of  passive 
congestion.  The  general  oedema  and  collection  of  fluid  in  the 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION    105 

thoracic  pericardial  and  peritoneal  cavities  are  referable  to  the 
chronic  congestion  and  to  the  associated  nephropathy. 

The  condition  in  the  lymph  nodes  is  an  interesting  one.  Red 
lymph  nodes,  known  as  haemo-lymph  nodes,  have  been  described  in 
post  peritoneal  tissue  of  various  animals,  including  man,  and  the 
presence  of  red  marrow  tissue  has  been  described  in  the  sinuses.  In 
the  condition  here  the  blood  in  the  sinuses  has  been  brought  by  the 
afferent  lymphatics  from  small  haemorrhages  in  the  tissues  resulting 
from  the  passive  congestion. 

In  chronic  thickening  of  the  capsule  of  the  spleen  the  formation 
of  the  hard  masses  described  is  not  uncommon  in  some  cases  extend- 
ing over  the  entire  surface,  in  others,  as  in  this  case,  in  foci.  They 
are  formed  of  dense,  sclerotic  tissue  arranged  in  laminae  and  con- 
taining few  cells. 

It  is  usual  to  have  in  such  cases  clinical  evidence  of  oedema  and 
passive  congestion  of  the  lungs,  but  there  is  no  mention  of  pulmon- 
ary .oedema  in  the  last  years  of  life.  This  is  probably  due  to  the 
fact  that  owing  to  the  weakness  of  the  right  heart  the  blood  pressure 
in  the  lungs  was  low. 

Of  further  interest  is  the  chronic  pancreatitis,  a  condition  not 
infrequently  found  at  autopsies  and  unsuspected  during  life.  This 
did  not  affect  the  Islands  of  Langerhans.  The  length  of  time  that 
the  individual  lived  with  such  marked  cardiac  disease  is  unusual. 
Favorable  conditions  for  him  were  the  absence  of  arterio-sclerosis 
and  of  fibrous  myocarditis. 


OTITIS  MEDIA  FOLLOWED  BY  PHLEBITIS  AND  THROMBUS 
OF  JUGULAR  VEIN  WITH  CONDITIONS  CONSEQUENT 
UPON  THIS 

Anatomical  Diagnoses.  Otitis  media;  Purulent  mas toiditis;  Throm- 
bophlebitis of  jugular  vein  and  left  lateral  sinus;  Multiple  sub- 
cutaneous abscesses;  Septic  infarction  of  lung  and  spleen;  Acute 
splenic  tumor;  Acute  vegetative  endocarditis  (mitral  valve); 
Cloudy  swelling  of  liver  and  kidneys;  Mastoid  operation  wound; 
Streptococcus  and  staphylococcus  infection. 

Male,  white,  age  18  years.  Autopsy  six  hours  post  mortem.  Body 
of  a  well-developed,  fairly  well-nourished  boy.  Rigor  mortis  present 
but  not  marked.  Body  still  warm.  Over  the  right  shoulder  and  both 


io6  PATHOLOGY 

elbows  are  large  fluctuating,  subcutaneous  abscesses.    On  the  left  side 
there  is  a  mastoid  operation  wound. 

Abdomen  is  normal,  free  from  fluid.  Mesenteric  lymph  nodes  are 
not  enlarged. 

Thorax.  Diaphragm  reaches  to  the  fourth  rib  on  the  right  side;  to 
the  fourth  interspace  on  the  left  side. 

Pleural  cavities  are  free  from  adhesions  and  contain  no  fluid. 

Pericardial  cavity  is  normal. 

Heart,  weight  260  grams.  Epicardium  and  myocardium  are  normal. 
Endocardium  is  normal.  The  aortic,  pulmonic  and  tricuspid  valves 
are  normal.  On  one  flap  of  the  mitral  valve  there  are  several  flattened, 
sessile,  button-like  vegetations  measuring  2  to  4  mm.  in  diameter. 
These  are  situated  near  but  not  at  the  edge  of  the  flap.  On  the  other 
flap  there  is  a  slightly  pedunculated  granulation  about  3  mm.  in  diam- 
eter and  5  mm.  long.  These  granulations  are  granular,  grayish,  some- 
what translucent  in  appearance,  and  appear  to  be  fairly  friable. 

Lungs.  Surface  of  both  lungs  smooth.  The  lungs  are  grayish  red 
anteriorly,  shading  to  dark  red  posteriorly.  Cut  surface  is  smooth, 
moist,  and  from  it  a  considerable  amount  of  frothy  fluid  can  be  expressed. 
Nowhere  can  consolidation  be  made  out.  In  the  upper  part  of  the  right 
lower  lobe,  in  the  posterior  region,  there  is  a  grayish  yellow  area,  about 
i  cm.  hi  diameter,  somewhat  irregular  in  contour,  which  is  visible  through 
the  pleura,  being  situated  immediately  subpleural.  Section  of  this 
shows  it  to  be  an  abscess  cavity.  No  other  abscess  is  to  be  found  in  the 
lungs.  The  bronchi  contain  a  moderate  amount  of  mucus  and  show 
slight  hyperaemia.  The  bronchial  lymph  nodes  are  somewhat  enlarged, 
grayish  red  on  section. 

Spleen,  weight,  410  grams.  The  spleen  does  not  lie  in  its  usual  posi- 
tion just  under  the  edge  of  the  ribs,  but  lies  crowded  back  where  it  is 
bound  by  quite  firm  fibrous  adhesions;  consequently  the  lower  border 
of  the  spleen  lies  well  above  the  costal  margin.  Near  one  end  there  is 
an  area  3  cm.  by  4  cm.,  which  is  gray  in  color,  and  here  the  tissue  is 
distinctly  softer  than  elsewhere.  Section  at  this  point  shows  a  roughly 
wedge-shaped  area  whose  center  is  softened  and  filled  with  a  pinkish 
gray  fluid,  and  in  whose  periphery  there  is  a  fairly  firm  tissue  of  the  same 
color.  This  is  quite  sharply  marked  off  from  the  dark  red  tissue  of  the 
surrounding  spleen.  At  the  other  end  of  the  spleen  there  are  one  or 
two  small  areas,  none  exceeding  i  cm.  in  diameter,  which  are  lighter, 
more  distinctly  yellow  in  color,  and  whose  centres  are  soft.  Spleen 
elsewhere  is  dark  red;  malpighian  bodies  indistinct.  From  the  cut 
surface  a  considerable  amount  of  pulp  is  easily  scraped. 
Stomach,  intestine  and  pancreas  normal. 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     107 

Liver,  weight,  1560  grams.  Is  smooth;  brown  in  color;  the  markings 
are  indistinct;  consistence  normal.  Gall  bladder  .normal.  Kidneys, 
weight,  370  grams.  Capsule  strips  very  readily  leaving  a  perfectly 
smooth  surface.  Cut  surface  of  cortex  appears  to  be  slightly  thicker 
than  normal  and  is  grayish  pink  in  color.  The  pyramids  are  darker, 
grayish  red,  with  indistinct  markings;  consistence  is  normal.  Adrenal 
glands  normal.  Bladder  normal. 

Aorta  normal. 

Organs  of  neck.  Continuing  the  surgical  incision  down  over  the 
sternal  notch  the  jugular  vein  is  laid  bare  and  slit  open.  At  a  point 
about  one-half  inch  above  the  clavicle  the  vein  contains  a  gray,  purulent 
material,  and  to  the  walls  of  the  vessel  is  adherent  a  thin  coating  of 
similar  color,  which  cannot  be  readily  stripped  off.  At  the  lowest  limit 
of  this  condition  there  is  a  small  amount  of  dark  red  clot,  below  which 
the  walls  of  the  vein  are  perfectly  smooth  and  no  clot  is  present.  This 
condition  can  be  traced  up  to  the  jugular  fossa,  and  by  removing  portions 
of  the  temporal  bone  can  be  traced  into  the  lateral  sinus  to  a  point  about 
on  a  level  with  the  upper  portion  of  the  mastoid  sinus.  Here  the  condi- 
tion ends.  Above  this  the  vein  contains  a  fairly  firm,  dark  red  clot  and 
has  smooth  walls.  In  the  mastoid  cells  there  is  a  small  amount  of 
purulent  material,  the  pus  everywhere  being  of  this  fluid  character.  The 
lymph  nodes  encountered  along  the  course  of  the  vein  are  somewhat 
enlarged  and  grayish  pink  in  color. 

Culture  made  from  lateral  sinus  shows  in  water  of  condensation  short 
chains  of  flattened  cocci  (streptococci)  and  scattered  round  cocci  (staphyl- 
ococci).  Surface  of  serum  shows  white  and  yellow  colonies  of  staphyl- 
ococcus  alb  us  and  aureus  respectively. 

REMARKS.  The  case  is  primarily  one  of  otitis  media  with  exten- 
sion of  the  infection  to  the  mastoid  cells  and  to  jugular  vein  produc- 
ing in  this  a  thrombophlebitis.  Such  an  extension  of  the  infection 
from  the  otitis  media  is  one  of  the  dangerous  complications  which 
may  occur  in  this  affection.  The  other  infections,  the  acute  endo- 
carditis, the  subcutaneous  abscesses  and  the  septic  infarction  of 
lung  and  spleen  are  all  the  result  of  the  following  blood  infection. 
Observe  the  character  of  the  infarction  in  the  lung  and  spleen.  To 
the  mechanical  factors  produced  by  the  emboli  there  is  added  the 
infection  with  softening  of  the  tissue.  The  cultures  have  shown  a 
mixed  infection,  the  streptococcus  is  probably  the  primary  agent 
and  the  staphylococcus  a  secondary  invader. 


io8  PATHOLOGY 

A  CASE  OF  ARTERIO-SCLEROSIS  WITH  FIBROUS  MYOCARDITIS 
AND  CARDIAC  ANEURYSM.    DEATH  FROM  PERITONITIS 

Anatomical  Diagnoses.  Extreme  coronary  sclerosis;  Chronic 
fibrous  myocarditis;  Cardiac  hypertrophy  and  dilatation;  Thin- 
ning of  a  portion  of  the  wall  of  the  left  ventricle  with  slight 
aneurysmal  dilatation;  Parietal  thrombosis  of  left  ventricle; 
Thrombosis  (embolism)  of  right  common  iliac  artery  and  its 
branches;  Amputation  of  right  leg  (for  gangrene);  Haemorrhagic 
infarction  of  both  lungs;  Chronic  passive  congestion  of  liver, 
spleen  and  kidneys;  Slight  chronic  diffuse  nephropathy;  Acute 
fibrinopurulent  peritonitis. 

Male,  white,  age  forty-four  years.  Body  well  developed,  well  nour- 
ished, 173  cm.  long.  Rigor  mortis  present,  but  slightly  developed. 
Pupils  equal,  and  slightly  dilated.  Marked  pallor  of  cutaneous  surface 
except  dependent  parts  which  show  slight  lividity.  Right  thigh  has 
been  amputated  at  the  lower  third.  Transverse  amputation  wound 
5  cm.  long,  closed  by  interrupted  sutures.  Wound  shows  externally 
slight  evidence  of  healing,  and  from  it  escapes  a  serosanguineous  fluid. 
In  lower  half  of  abdomen  is  a  small  puncture  wound,  closed  by  collodion 
dressing. 

Abdomen.  On  incising  abdomen,  there  is  an  escape  of  a  considerable 
amount  of  gas  having  a  fecal  odor;  with  this  there  is  marked  collapse  of 
the  previously  distended  abdomen.  The  abdomen  contains  a  consider- 
able amount  of  greenish-yellow  purulent  fluid  in  which  float  numerous 
flocculi  of  fibrin.  Three  or  four  hundred  cubic  centimeters  of  such  fluid 
were  sponged  out  of  the  cavity.  Peritoneal  surfaces  are  deeply  injected; 
in  many  places  being  bright  red  in  color.  Adjacent  loops  of  intestine 
are  everywhere  interadherent  by  a  sticky,  plastic  layer  of  fibrin,  separat- 
ing with  moderate  ease.  One  loop  of  intestine  low  down  in  the  ileum  is 
quite  firmly  adherent  to  the  anterior  abdominal  wall  above  and  to  the 
right  of  the  umbilicus.  Separation  of  this  adhesion  causes  a  tear  in  the 
intestine  which  at  this  point  is  distinctly  friable.  Apparently  here  there 
is  a  fairly  firm  fibrous  adhesion,  as  opposed  to  the  fibrinous  adhesions 
elsewhere.  In  very  many  places  the  peritoneal  surface  of  the  stomach, 
intestines,  liver  and  spleen  is  covered  with  a  layer  of  fibrin  1-2  mm. 
thick,  rather  elastic,  grayish  or  yellow  gray  in  color,  and  peeling  away 
fairly  easily  from  the  underlying  serosa  which  is  brightly  injected  and 
smooth.  Throughout  the  large  intestine  the  appendices  epiploicae  are 
congested,  often  covered  with  fibrin,  and  on  section  show  small  lobules 
of  yellow  fat  separated  by  lines  of  injected  tissue.  Here  and  there  the 
serous  surface  of  the  large  intestine  is  covered  by  flakes  of  fibrin. 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     109 

Appendix  is  free  from  adhesions,  lies  in  right  iliac  fossa  and  its  serosa 
shares  the  general  condition  of  the  other  abdominal  viscera.  The  pelvic 
fossa  is  more  deeply  congested  than  other  portions  of  the  abdominal 
cavity  and  fibrin  is  more  abundant  in  this  region.  Nowhere  are  there 
definite  walled-off  pus  pockets.  Mesentery  is  likewise  congested. 
Surface  shows  here  and  there  exudate,  and  the  mesenteric  lymph  nodes 
buried  in  mesenteric  fat  are  distinctly  enlarged,  succulent,  pink  gray  on 
cut  surface. 

Thorax.  Diaphragm  is  not  depressed.  Both  pleural  cavities  are 
free  from  fluid  and  adhesions.  Pericardial  cavity  free  from  fluid. 
Peritoneum  smooth  and  glistening. 

Heart  is  large.  Weight,  535  grams.  Left  ventricle  is  firmly  con- 
tracted. Right  ventricle  is  less  so.  Right  auricle  is  considerably  dis- 
tended. Pericardial  surface  shows  numerous  ecchymoses,  varying  from 
one  to  several  millimeters  in  diameter,  generally  distributed,  but  very 
much  more  numerous  along  auriculo-ventricular  depression  and  along 
the  descending  portion  of  the  left  coronary  artery.  Both  coronary 
arteries  can  be  easily  palpated  as  hard  nodular  tubes  lying  beneath  the 
serosa,  and  their  course  can  be  thus  traced  almost  down  to  the  apex  of 
the  heart.  Left  side  of  the  heart  contains  a  small  amount  of  easily 
separated  post  mortem  clot.  Right  side  of  heart  contains  considerably 
more  of  the  same  kind  of  clot.  Both  auricular  appendages  are  entirely 
free  from  thrombi  as  is  also  the  right  ventricle.  In  the  left  ventricle, 
largely  filling  up  the  apical  portion,  there  is  a  parietal  thrombus  measur- 
ing 4  by  3  by  i  cm.  This  is  firmly  attached  to  the  anterior  and  right 
lateral  portions  of  the  ventricle  from  the  apex  upward.  It  is  ovoid, 
pinkish  gray  in  color,  flecked  with  small  areas  of  darker  red.  Its  surface 
is  irregularly  pitted,  but  there  is  no  evidence  of  a  portion  having  recently 
broken  away.  Incision  into  this  thrombus  shows  the  central  part  to  be 
somewhat  softened,  though  still  solid  in  consistency,  and  much  paler  in 
color  than  the  periphery.  The  post  mortem  clots  described  above 
separate  easily  from  its  surface  and  from  the  cardiac  surfaces,  while  this 
is  firmly  adherent  and  attempts  at  removal  to  tear  the  clot  rather  than 
separate  it.  Elsewhere  the  cardiac  surfaces  are  smooth.  Valves  are  nor- 
mal, except  the  mitral  which  shows  a  few  yellow  plaques  along  its  base,  in 
nowise  interfering  with  the  closing  of  the  valve.  Mitral  valve  n  cm., 
tricuspid  valve,  12  cm.,  aortic  valve  7  cm.,  pulmonic  valve  7  cm.  in  circum- 
ference, left  ventricle  1.3  cm.  thick  at  a  point  shortly  below  mitral  ring. 
Right  ventricle  in  a  similar  place  0.5  cm.  thick.  Sections  made  through 
the  ventricle  at  the  point  of  the  attachment  of  the  thrombus  show  that 
the  wall  is  here  reduced  in  thickness  in  places  to  0.5  c.m.,  and  instead  of 
the  red  of  the  cardiac  muscle  elsewhere  is  mottled  grayish  in  color, 


no  PATHOLOGY 

leathery  in  consistency,  and  in  the  portion  nearest  the  rhombus  is  gray 
without  any  mixture  of  red,  and  this  tissue  seems  to  be  directly  continu- 
ous with  the  thrombus,  at  least  no  sharp  line  of  demarkation  is  apparent, 
though  no  bands  of  tissue  can  be  traced  into  the  thrombus.  Sections 
elsewhere  through  the  wall  of  the  ventricle  show  scattered  areas  slightly 
depressed,  red  or  gray  in  color,  and  measuring  2-3  mm.  in  diameter. 
Both  coronary  arteries  arise  by  unobstructed  lumina  from  the  aorta, 
and  for  a  very  short  distance  are  smooth.  However,  almost  immediately 
they  become  converted  into  thickened  tubes,  showing  at  close  intervals 
irregular  nodules  of  thickening  of  a  grayish  yellow  color,  many  of  which 
are  calcified  and  through  which  a  lumen  can  be  traced  with  difficulty. 
In  many  places  these  nodules  occupy  one  side  of  the  lumen  and  section 
of  the  vessel  shows  a  semilunar  rather  than  a  round  opening.  This  con- 
dition of  extreme  sclerosis  can  be  traced  in  all  branches  of  both  coronaries 
down  to  their  finer  ramifications.  In  none  could  complete  occlusion  be 
made  out.  There  is  no  evidence  of  thrombus  obstruction,  yet  the  lumen 
is  undoubtedly  reduced  in  many  places. 

Lungs.  Surface  of  both  is  smooth.  Lungs  are  air-containing  for  the 
most  part.  Posterior  portions  moderately  injected;  anterior  parts 
much  paler.  There  is  a  moderate  degree  of  carbon  pigmentation.  At 
the  upper  portion  of  the  right  upper  lobe  there  is  a  slightly  depressed, 
puckered  area  from  which  bands  of  connective  tissue  extend  a  short 
distance  into  the  lung.  No  areas  of  caseation  or  calcification  at  this 
point.  In  the  anterior  part  of  the  right  lower  lobe  there  is  a  firm,  cir- 
cumscribed, dark  red  area  4  by  3  by  2  cm.,  sharply  separated  from  the 
adjoining  lung. 

In  the  posterior  portion  of  the  lower  part  of  the  left  lower  lobe  there 
are  similar,  less  sharply  defined,  less  firm,  but  solidified  areas,  dark  red 
in  color,  and  in  toto  of  slightly  greater  area  than  the  one  described  in  the 
other  lung.  Dissection  of  the  pulmonary  vessels  to  these  areas  reveal 
small  pulmonary  arteries  occluded  by  greyish-red,  granular,  rather 
friable  clots. 

Spleen.  Is  somewhat  enlarged,  dark  red  in  color.  Cut  surface  is 
dark  gray  red.  Consistency  firm.  Malpighian  bodies  are  just  visible 
as  small  grayish  points. 

Stomach  is  dilated  to  a  moderate  degree,  and  filled  with  a  sour  smelling 
fluid.  Mucous  membrane  appears  normal.  Duodenum  beginning  at 
the  pylorus  and  extending  well  down  below  the  bile  papilla  shows  closely 
set  foci  1-2  mm.  in  diameter,  of  bright  red  congestion.  No  other  change 
apparent.  Intestinal  tract  below  this  appears  normal  throughout  but 
for  the  changes  already  described  in  the  peritoneal  surface  and  which 
extend  for  a  very  short  distance  into  the  wall  of  the  intestine. 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     in 

Pancreas  is  firm;  tabulations  distinct.    No  other  change  evident. 

Liver  is  slightly  enlarged;  projects  a  little  below  the  costal  margin  of 
the  right  mammary  line.  Its  left  lobe  is  proportionately  large,  and 
extends  somewhat  lower  than  normal  in  the  median  line.  The  surface 
of  the  liver  is  perfectly  smooth.  The  notch  of  the  gall  bladder  is  a  little 
deeper  than  usual,  and  the  tip  of  the  gall  bladder  can  be  seen  lying  in  the 
notch,  projecting  a  trifle  above  the  surface  of  the  liver.  Cut  surface  of 
the  liver  is  grayish  brown  in  color.  Markings  are  distinct,  centers  of 
the  lobules  apparently  being  congested. 

Gall  bladder  is  normal. 

Kidneys  of  about  normal  size.  Capsule  strips  easily  from  a  slightly 
granular  surface;  of  a  dusky  gray-red  color.  Cut  surface  is  of  the  same 
dusky  hue.  Cortex  slightly  thinned.  Markings  distinct. 

Adrenals  normal. 

Bladder  normal. 

Aorta.  Beginning  from  the  heart  and  extending  well  down  into  the 
thoracic  region  the  aorta  shows  only  here  and  there  scattered,  yellowish, 
slightly  elevated  plaques  of  thickening.  In  the  lower  half  of  the  abdomi- 
nal aorta  the  surface  is  irregularly  roughened;  here  and  there  are  small 
areas  with  superficial  loss  of  surface,  and  in  the  wall  are  numerous  irregu- 
lar, calcified  plaques.  The  left  common  iliac  artery  shows  small  scattered 
areas  of  thickening,  here  and  there  a  calcified  area.  The  right  common 
iliac  beginning  at  the  bifurcation  and  extending  about  3  cm.  is  filled  with 
a  dark  red,  nonadherent  blood  clot.  From  this  point,  and  as  far  as  can  be 
reached  by  an  interabdominal  dissection  all  branches  are  filled  by  blood 
clot  adherent  to  the  walls  of  the  vessel  and  varying  in  color  from  dark 
red  to  gray.  Central  part  of  this  clot  is  here  and  there  softened  and  is 
distinctly  friable.  In  making  sections  across  the  vessels  at  various  points 
a  few  areas  of  calcification  are  encountered  in  the  wall  of  the  vessel,  but 
parts  examined  do  not  show  any  extensive  degree  of  arterio-sclerosis, 
and  the  lumen  of  the  larger  vessels  is  certainly  in  no  way  obstructed 
except  by  the  clot. 

The  renal  arteries  and  the  arteries  coming  off  from  the  cceliac  axis  are 
free  from  blood  clot  and  do  not  show  any  evident  sclerosis.  Their  dis- 
section was  followed  to  the  spleen,  kidneys,  and  in  several  branches  to 
the  mesenteric  border  of  the  small  intestine. 

The  inferior  vena  cava  is  not  obstructed  by  clot,  and  appears  normal. 

Coverslips  and  cultures  made  from  the  peritoneal  exudation  gave 
staphylococcus  aureus. 

REMARKS.  The  right  thigh  was  amputated  at  lower  third  for  gan- 
grene several  days  before  death.  Following  the  amputation  there 


112  PATHOLOGY 

was  accumulation  of  gas  in  intestines  for  the  relief  of  which  puncture 
was  made.  The  interrelation  of  the  pathological  conditions  is 
probably  this :  There  first  occurred  a  general  arterio-sclerosis  most 
marked  in  the  coronary  arteries  and  producing  calcification  in  arte- 
ries of  extremities.  Heart  hypertrophy  due  to  this  and  the  chronic 
nephropathy  followed.  The  extreme  sclerosis  of  coronary  arteries 
led  to  extensive  myocarditis,  particularly  at  the  apex  of  left  ven- 
tricle. Dilatation  and  production  of  partial  cardiac  aneurysm 
occurred  at  this  point.  Owing  to  the  roughening  of  surface  and 
the  slowing  of  current,  a  large  endo-cardial  thrombus  formed.  In 
the  majority  of  cases,  thrombi  form  at  such  places  of  myocardial 
dilatation.  From  this  an  embolus  was  given  off  which  plugged 
the  femoral  artery  on  the  right  side  and  produced  gangrene.  This 
action  of  the  embolus  was  facilitated  by  the  arterio-sclerosis  which 
prevented  compensatory  dilatation  of  the  collateral  vessels.  The 
wound  did  not  heal  and  probably  became  infected.  Although  the 
conditions  of  the  autopsy  did  not  permit  examination  of  the  leg, 
it  is  almost  certain  that  a  thrombus  was  formed  in  the  femoral  vein 
on  the  same  side  and  from  this  the  emboli  which  led  to  the  infarc- 
tions of  the  lung  were  derived.  To  this  was  superadded  the  acute 
peritoneal  infection  which  followed  the  abdominal  puncture.  The 
autopsy  did  not  show  the  site  of  the  puncture  into  the  intestine, 
but  this  was  probably  at  the  point  where  the  intestine  subsequently 
became  adherent  to  the  anterior  abdominal  wall.  The  small 
ecchymoses  on  the  pericardium  were  associated  with  the  infection. 


SUDDEN  DEATH  FROM  PULMONARY  EMBOLISM  FOLLOWING 
THROMBOSIS  OF  ILIAC  VEIN 

Anatomical  Diagnoses.  Operation  wounds  in  both  iliac  regions; 
Colon  bacillus  infection  on  right  side;  Thrombosis  of  spermatic 
veins;  Thrombus  of  right  iliac  vein;  Embolus  in  left  pulmonary 
artery. 

White,  male,  age  thirty-nine  years.  Operated  on  for  double  inguinal 
hernia  four  days  before  death.  Two  days  after  operation  increase  in 
temperature  with  pain  in  right  iliac  region.  Death  occurred  suddenly 
two  days  later. 

Body  well  developed  and  well  nourished.  Rigor  mortis  is  present. 
Moderate  post-mortem  lividity.  In  each  inguinal  region  there  is  an 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     113 

incised  wound,  8  cm.  in  length,  extending  in  the  direction  of  Poupart's 
ligament,  and  closed  by  sutures.  On  opening  the  wounds,  the  tissues 
on  the  left  side  are  dry  and  clean,  the  wound  surfaces  lightly  adherent  by 
fibrin.  On  the  right  side  the  tissues  in  the  wound  are  bathed  in  a  thin, 
red,  cloudy  fluid  and  the  deeper  tissues  are  cedematous.  The  right  sper- 
matic cord  is  dark  red  in  color,  is  nodular  on  palpation  and  contains 
fibrinous  exudation.  In  the  spermatic  veins  are  adherent,  pale  red 
thrombi. 

The  peritoneum  is  smooth  and  glistening.  There  is  some  injection 
of  the  blood  vessels  along  the  lines  of  incisions,  but  there  is  no  exudation. 
The  mesenteric  lymph  nodes  are  normal.  In  the  right  common  iliac 
vein  is  a  light  gray-red  thrombus,  adherent  to  the  wall  at  one  side,  and 
extending  upward  to  4  cm.  above  the  bifurcation  and  downward  for  a 
distance  of  3  cm.  into  the  two  branches  of  the  vein.  The  upper  end  of 
the  thrombus  is  capped  by  a  pointed,  dark  red,  soft  clot,  sharply  outlined 
from  the  thrombus  and  easily  separated. 

The  heart  is  normal  in  size  and  in  structure.  The  left  pulmonary 
artery  is  occluded  by  a  firm,  convoluted,  non  adherent  embolus  of  the 
same  character  and  of  the  same  diameter  as  the  thrombus  in  the  iliac  vein. 

The  other  organs  of  the  body  normal. 

Smears  and  cultures  from  the  operation  wound  on  the  right  side 
showed  colon  bacilli. 

REMARKS.  The  case  is  a  simple  one.  The  thrombosis  of  the 
iliac  vein  is  secondary  to  infection  of  the  wound  on  the  right  side 
and  is  due  to  infection  of  the  vein  wall.  Thrombi  are  not  infre- 
quent after  surgical  operations  in  the  peritoneal  cavity  and  may 
result  from  congestion  and  slowing  of  the  circulation  without  any 
infection.  The  embolus  was  broken  off  from  the  thrombus  and 
its  lodgment  in,  and  sudden  occlusion  of,  the  left  pulmonary  artery 
produced  sudden  death. 

GENERAL  ARTERIO-SCLEROSIS,  FOCAL  IN  CHARACTER  WITH 
SUDDEN  DEATH  DUE  TO  DISEASE  OF  CORONARY 
ARTERIES 

Anatomical  Diagnoses.  General  arterio-sclerosis  most  marked  in 
coronary  arteries  of  heart;  Fibroid  myocarditis;  Chronic  peri- 
tonitis with  adhesions. 

White,  male,  age  forty-eight  years.  The  individual  was  a  man  of  very 
athletic  habit,  a  climber  of  mountains,  a  skillful  swimmer  who  was 
accustomed  to  swim  in  the  sea  for  hours  and  who  excelled  in  most  athletic 


H4  PATHOLOGY 

exercises.  For  two  years  past  has  not  been  able  to  lead  so  active  and 
athletic  a  life  as  formerly.  This  particularly  felt  in  exercises  which  were 
prolonged.  On  the  day  of  his  death,  while  engaged  in  a  game  of  hand- 
ball, he  staggered,  leaned  for  a  moment  against  the  side  of  the  court,  fell 
and  when  his  companion  reached  him  he  was  dead. 

Autopsy  twenty-four  hours  after  death.  The  body  strongly  built, 
the  thorax  broad,  muscles  well  developed.  General  rigor  mortis.  Some 
congestion  of  dependent  parts  of  the  body.  In  the  abdomen  in  the  right 
iliac  region  is  a  small  cicatrix.  The  subcutaneous  fat  small  in  amount, 
muscles  dark  red.  In  the  peritoneum,  corresponding  to  the  site  of  cica- 
trix in  the  abdomen,  there  are  numerous  fibrous  adhesions  in  the  region 
about  the  caecum  and  appendix.  The  appendix  is  16  cm.  long  and  passes 
downwards,  backwards  and  upwards  beneath  the  ascending  colon,  its 
distal  end  in  the  vicinity  of  the  right  kidney.  It  is  free  for  a  distance  of 
8  cm.,  then  passes  into  a  pocket  of  peritoneum  2  cm.  deep,  and  for  the 
remainder  of  its  length  lies  entirely  in  the  post-peritoneal  tissue.  The 
liver  and  spleen  free  from  adhesion. 

Both  lungs  free  from  adhesions.  On  section  deeply  congested,  no 
oedema. 

The  heart  weighs  370  grams.  The  right  side  is  greatly  dilated,  the 
left  slightly.  The  valves  normal.  The  myocardium  in  general  of  a  dark 
red  color,  but  throughout  the  left  ventricle  and  in  the  interventricular 
septum  there  are  numerous  white  or  pale  yellow  streaks. 

The  coronary  arteries  are  of  normal  size  at  their  exit  from  the  aorta; 
but  in  their  course  show  a  high  degree  of  arterio-sclerosis  which  is  most 
marked  in  the  left  coronary  artery.  The  sections  of  the  artery  show  a 
general  thickening  of  the  walls  which  is  intensified  in  foci  where  the  thick- 
ening is  lateral.  They  are  free  from  thrombi  or  emboli  and  where 
thickening  is  most  marked  the  calibre  is  very  narrow.  This  condition 
extends  into  the  smallest  branches  which  can  be  traced.  The  situation 
of  the  areas  of  myocarditis  correspond  to  the  distribution  of  the  arteries 
in  which  there  is  a  marked  degree  of  diseases.  The  transverse  branch 
of  the  right  coronary  artery  shows  a  similar  condition.  The  aorta  shows 
definitely  circumscribed,  nodular  plaques  most  marked  in  the  arch  and 
thoracic  portions.  The  wall  between  these  plaques  shows  here  and  there 
white  or  yellow  streaks,  but  is  not  thickened.  A  marked  degree  of  focal 
nodular  thickening  is  seen  in  the  innominate,  the  sub  clavian  and  carotid 
arteries.  The  arteries  at  the  base  of  the  brain  are  normal.  The  arteries 
supplying  the  abdominal  organs  show  a  moderate  degree  of  thickening. 

Brain,  liver,  kidneys,  adrenal,  intestinal  canal  and  genitalia  are  normal. 

The  microscopical  examination  of  the  organs  with  the  exception  of 
the  heart  showed  minor  degrees  of  sclerosis  in  the  small  distributing 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     115 

arteries.  Sections  of  the  large  arteries  show  very  extensive  degeneration 
and  rupture  of  media  with  great  thickening  of  the  corresponding  intima. 
The  most  marked  degree  of  degeneration  is  found  in  the  coronary  arteries 
of  the  heart.  Where  the  nodular  thickening  is  most  marked  there  is 
complete  destruction  of  media.  Examinations  for  fat  showed  very 
marked  fatty  degeneration  everywhere. 

REMARKS.  The  weight  of  the  heart,  370  grams,  is  somewhat 
above  the  average,  but  is  normal  for  an  individual  leading  a  very 
athletic  life.  It  is  not  improbable  that  the  arteriosclerosis  of  the 
coronary  arteries  interfered  sufficiently  with  the  nutrition  of  the 
heart  to  produce  some  loss  in  reserve  force,  some  time  previous  to 
death.  In  the  present  condition  of  the  coronary  arteries  it  is 
probable  that  the  nutritive  reserve  of  the  heart  was  seriously 
diminished.  The  areas  of  fibrous  myocarditis  show  that  in  places 
complete  destruction  of  myocardium  with  substitution  of  fibrous 
tissue  has  taken  place.  The  sudden  death  is  to  be  attributed  to 
the  instant  exhaustion  of  the  imperfectly  nourished  muscular 
tissue.  The  arterio-sclerosis  is  unusual  in  the  extent  of  the  lesions 
and  in  their  marked  focal  character  particularly  those  in  the  aorta. 
There  is  no  indication  of  syphilis.  The  small  arteries  of  the  body 
are  in  good  condition,  though  occasionally  an  artery  is  found  as 
in  one  of  the  arcuate  arteries  of  the  kidney  which  shows  a  condition 
similar  to  that  in  the  aorta.  The  cicatrix  in  the  abdominal  wall 
is  the  result  of  a  previous  operation,  for,  but  without  resulting  in, 
appendectomy. 


HEART  HYPERTROPHY  WITH  ENDOCARDIAL  THROMBI, 
ARTERIO-SCLEROSIS  AND  CHRONIC  NEPHROPATHY 

Anatomical  Diagnoses.  General  arterio-sclerosis;  Thrombosis  of 
coronary  artery  with  infarction  of  heart ;  Heart  hypertrophy  and 
dilatation;  Multiple  mural  thrombi  in  heart;  Chronic  diffuse 
nephropathy  with  recent  and  old  infarction;  Pulmonary  embolism 
and  infarction;  Healed  pulmonary  tuberculosis;  General  passive 
congestion;  (Edema;  Ascites;  Hydrothorax  and  hydroperi- 
cardium. 

Male,  white,  age  fifty  years.  Body  that  of  a  short,  well  built,  rather 
stout  man.  Subcutaneous  fat  fairly  abundant.  Lymph  nodes  not 
palpable.  Rigor  mortis.  There  are  about  15  or  20  discrete  red  papules 


n6  PATHOLOGY 

i  to  2  mm.  in  diameter  scattered  over  the  anterior  chest.  (Small  capil- 
lary telangiestases.)  Slight  post  mortem  lividity.  Slight  oedema  of 
lower  extremities.  Abdomen  distended. 

Peritoneum.  Subcutaneous  tissue  somewhat  oedematous.  The  peri- 
toneal cavity  contains  about  300  c.c.  of  pale,  clear  fluid.  Peritoneum 
smooth.  Stomach  and  intestines  distended. 

Pleurae.  Both  internal  mammary  arteries  are  thickened.  Each 
pleural  cavity  contains  about  700  c.c.  of  pale  amber  fluid.  There  are 
dense,  thick  adhesions  over  the  apex  of  the  right  lung. 

Heart.  The  pericardium  contains  50  c.c.  of  clear,  pale  fluid.  No 
adhesions.  The  heart  is  large,  weight,  770  grams.  The  right  auricular 
appendage  is  entirely  filled  with  a  pale  red  friable  adherent  thrombus. 
Similar  small  adherent  thrombi  are  found  over  interventricular  septum 
in  right  ventrical  between  the  muscle  bands.  These  thrombi  present 
much  variation  hi  color  and  in  character.  Some  of  them  are  red,  others, 
on  section,  red  and  white,  and  others  entirely  white;  the  centres  of  some 
of  the  larger  white  thrombi  are  softened. 

The  aortic  cusps  show  a  moderate  thickening  of  their  free  margin  and 
a  small  calcareous  nodule  occupying  the  position  of  the  corpus  arantii 
of  one  of  the  cusps.  The  coronary  arteries  show  advanced  sclerosis  and 
calcification.  The  lumen  of  the  descending  branch  of  the  left  coronary 
artery  is  occluded  2  mm.  from  its  origin  by  a  dark-brown  friable  adherent 
thrombus.  Beyond  this  the  inner  half  of  two-thirds  of  the  posterior 
wall  of  the  left  ventrical  is  darker  than  the  surrounding  myocardium  and 
contains  large  pale  or  grayish-yellow  areas,  most  numerous  and  distinct 
immediately  beneath  the  endocardium.  The  papillary  muscle  attached 
to  this  region  is  soft,  pale  yellow  and  its  base  is  surrounded  by  mural 
thrombi. 

The  aorta  shows  extensive  arterio-sclerotic  thickening  both  in  patches 
and  diffuse.  In  the  abdominal  aorta  most  marked  above  the  bifurcation 
there  is  extensive  calcification  and  a  number  of  ulcers  with  irregular 
undermined  edges.  All  the  large  arteries  show  marked  diffuse  and 
nodular  sclerosis. 

Lungs.  At  the  apex  of  the  left  lung  the  pleura  is  thickened  and 
puckered.  On  the  surface  adjacent  to  the  pericardium  there  are  a 
number  of  small  grayish  or  yellow,  firm  nodules  i  to  2  mm.  in  diameter, 
gritty  on  section  with  cheesy  centres.  These  lie  just  beneath  the  pleura. 
On  section  the  lung  is  of  a  diffuse  brick  red  color  and  considerable  fluid 
oozes  from  the  cut  surface,  but  the  tissue  is  crepitant  throughout.  At 
the  apex  of  the  right  lung  is  a  large  nodule  2  cm.  in  diameter,  the  centre 
containing  a  grayish-yellow  material  of  the  consistency  of  putty;  around 
this  there  is  a  dense  fibrous  capsule  with  fibrous  extensions  into  the  sur- 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     117 

rounding  lung  tissue.  The  pleural  surface  around  the  nodule  is  thickened 
and  cicatricial.  The  entire  lung  is  heavier,  more  congested  and  contains 
more  fluid  than  the  left.  On  the  posterior  surface  of  the  lower  lobe  there 
is  a  solid  area  4  by  3  by  2  cm.  sharply  separated  from  the  adjoining  lung 
tissue,  which,  by  comparison,  is  deeply  depressed  below  the  level  of  this 
area.  The  area  is  dark  red  in  color.  The  cut  surface  is  smooth  and  dark 
red  in  color,  and  sharply  separated  from  the  adjoining  congested  lung 
tissue.  In  shape  the  area  is  triangular,  the  base  on  the  pleural  surface. 
The  pulmonary  artery  leading  to  this  area  is  occluded  by  an  adherent 
pale  red  embolus.  The  bronchial  lymph  nodes  are  enlarged,  deeply 
pigmented  and  injected  and  contain  caseous  and  calcified  masses. 

Liver,  weight,  1515  grams.  Surface  deep  brown,  slightly  irregular, 
and  finely  mottled  with  dark  and  paler  areas.  The  cut  surface  shows 
this  nutmeg  mottling  more  plainly. 

Spleen,  weight,  150  grams.    Surface  dark  red  and  slightly  wrinkled, 
consistency  increased.    Malpighian  bodies  and  trabeculae  prominent. 
Pancreas  normal. 

Kidneys,  weight,  330  grams.  Adherent  to  perinephritic  fat.  Capsules 
nonadherent.  In  each  kidney  beneath  the  capsule  there  are  a  few  de- 
pressed areas  from  0.5  to  i  cm.  in  diameter  with  yellow  centres.  These 
show  on  section  a  grayish-red  cicatricial  periphery  sharply  separated  from 
the  yellow  centres.  In  the  lower  pole  of  the  left  kidney  is  a  slightly  ele- 
vated, pale  yellow  area  2  by  2^  cm.  with  an  irregular  and  intensely  red 
border.  On  section  the  area  is  firm,  rather  dry,  irregularly  triangular  in 
shape,  the  apex  slightly  extending  into  the  pyramid.  On  the  kidney 
section  the  arterial  branches  are  prominent.  The  cortex  is  somewhat 
reduced  in  size,  the  consistency  increased,  the  markings  obscure. 
Adrenals  normal. 
Genitalia  normal. 

Gastro-intestinal  tract.  Mucosa  of  stomach  and  intestines  deeply 
injected. 

Brain  and  cord  not  examined. 

The  microscopic  examination  of  all  the  organs  shows  advanced  arterio- 
sclerosis most  marked  in  arteries  from  J  to  ^  mm.  in  diameter.  In  many 
of  these  there  can  be  seen  only  traces  of  the  media,  the  greatly  thickened 
wall  being  formed  by  intima  only.  The  heart  shows,  apart  from  the 
area  of  infarction,  a  general  and  diffuse  fibrous  myocarditis.  The 
infarcted  area  shows  necrosis  and  fragmentation  of  the  muscle  fibres 
and  infiltration  with  polynuclear  leucocytes. 

Throughout  the  liver  the  cells  in  the  centres  of  the  lobules  are  in  part 
necrotic,  in  part  they  have  wholly  disappeared  and  in  their  place  there 
is  extensive  haemorrhage. 


Ii8  PATHOLOGY 

REMARKS.  The  case  presents  a  variety  of  conditions  some  of 
which  are  closely  interrelated.  There  is  an  old  tuberculosis  of 
the  lungs,  the  length  of  time  since  the  infection  indeterminate. 
The  lesions  have  become  completely  enclosed  in  cicatricial  tissue 
and  there  has  been  extension  to  the  bronchial  glands  only.  The 
heart  hypertrophy  is  to  be  referred  to  the  chronic  nephropathy  and 
arterio-sclerosis,  the  tripos  being  a  common  one.  The  extensive 
formation  of  thrombi  in  the  heart  is  associated  with  the  dilatation, 
the  diminished  rapidity  of  flow,  the  increased  irregularity  of  the 
surface  and  the  effect  of  the  myocarditis.  The  arterio-sclerosis 
of  the  coronary  arteries  which  is  the  cause  of  the  myocardial  de- 
generation is  a  part  of  the  general  arterial  disease.  The  emboli 
in  the  lung  came  from  the  thrombi  in  the  right  side,  and  the  infarc- 
tion following  the  embolus  is  due  to  the  increased  pressure  in  the 
pulmonary  veins  produced  by  the  dilatation  of  the  left  heart  and 
relative  mitral  insufficiency.  The  infarctions  in  the  kidney  result 
from  embolism  of  branches  of  the  renal  artery.  The  increased 
venous  pressure  has  led  to  an  increase  in  the  tissue  fluid  shown  by 
the  oedema  and  the  accumulation  of  fluid  in  the  body  cavities. 

CASE  OF  ANEURYSM  OF  ARCH  OF  AORTA  WITH  RUPTURE 

Anatomical  Diagnoses.  Aneurysm  of  ascending  arch  of  aorta  with 
rupture;  Erosion  of  sternum;  Haemorrhage  into  subcutaneous 
tissue  with  rupture  through  skin;  Hsemorrhagic  infiltration  of 
tissue  of  anterior  chest  wall. 

Male,  white,  age  fifty-two  years.  Body  well  developed,  well  nour- 
ished and  muscular.  Rigor  mortis.  Slight  post  mortem  lividity.  In 
the  median  line  on  the  anterior  surface  of  the  chest  is  a  hemispherical 
swelling,  which  projects  n  cm.  above  the  body  surface  and  has  a  circum- 
ference at  the  base  of  40  cm.  The  surrounding  skin  for  a  distance  of 
5  to  10  cm.  is  cedematous.  The  skin  from  the  anterior  borders  of  the 
axilla  and  the  root  of  the  neck  as  far  down  as  the  umbilicus  is  yellow, 
with  slight  greenish  tinge.  The  surface  of  the  tumor-like  swelling  is 
irregular  and  knobby.  Just  to  the  right  of  the  median  line  there  is  an 
irregular  opening  and  below  this  a  smaller  opening  from  both  of  which 
a  soft  red  blood  clot  projects.  The  subcutaneous  tissue  of  the  chest  and 
upper  abdomen  is  irregular,  infiltrated  with  blood  and  fibrin. 

Peritoneum.  Surface  smooth  and  glistening.  The  left  lobe  of  the 
liver  is  adherent  to  the  diaphragm  by  loose,  tough,  fibrous  bands.  The 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     119 

intestines  are  pale  and  distended  with  gas.  (The  sternum  is  disarticu- 
lated, the  trachea  and  oesophagus  cut  across,  and  the  thoracic  contents 
with  the  sternum  and  aorta  removed  in  mass.)  The  aorta  opened 
posteriorly  shows  a  few  yellowish  patches  in  abdominal  portion,  and 
considerable  sclerosis  about  the  origin  of  the  cceliac  axis.  In  the  upper 
9  cm.  of  the  thoracic  aorta  there  is  marked  sclerosis  and  calcification, 
chiefly  on  anterior  surface,  and  above  this  the  surface  is  irregularly 
thickened  with  cicatricial  wrinkling  and  with  but  little  calcification. 
The  great  vessels  given  off  from  the  arch  are  hi  high  degree  sclerosed  and 
have  small  flat  areas  of  calcification  on  the  surface.  The  aorta  from  a 
point  15  cm.  from  the  aortic  valve  to  the  origin  of  the  left  subclavian 
forms  a  large  aneurysmal  sac,  20  cm.  in  circumference.  The  inner  sur- 
face of  this  is  irregular  and  contains  numerous  yellow-white  calcareous 
plaques.  The  sac  anteriorly  is  adherent  to  the  sternum  from  the  lower 
border  of  the  first  rib  downward  to  about  the  middle.  The  inner  surface 
of  the  sternum  is  extensively  eroded  and  completely  destroyed  over  an 
area  6  cm.  in  diameter,  where  it  is  replaced  by  a  dense  fibrous  tissue, 
forming  the  anterior  wall  of  the  aneurysm.  In  this  there  is  an  opening 
2  cm.  in  diameter  forming  a  communication  between  the  cavity  of  the 
aneurysm  and  a  large  cavity  beneath  the  skin  filled  with  coagulated 
blood.  All  the  tissues  of  the  anterior  chest  wall  are  infiltrated  with  blood 
and  in  several  places  these  are  distinct  cavities  filled  with  clots.  There 
is  also  a  large  haemorrhagic  infiltration  of  the  pleura  between  the  first  and 
second  rib. 

Heart.  The  pericardial  cavity  in  places  is  obliterated  by  adhesions. 
The  heart  slightly  enlarged,  the  valves  normal. 

The  lungs  and  other  organs  of  the  body  unimportant. 

REMARKS.  There  is  marked  arteriosclerosis,  chiefly  of  arch 
and  thoracic  aorta  and  of  the  large  arteries  given  off  from  arch. 
The  aneurysmal  dilatation  is  fusiform  and  involves  the  entire  cir- 
cumference of  the  aorta,  but  the  chief  dilatation  is  of  the  anterior 
wall.  With  the  continuing  enlargement  it  came  in  contact  with  the 
sternum  and  adherent  to  this  around  the  area  of  contact.  The 
arterial  wall  in  contact  with  the  sternum  and  the  periosteum  became 
necrotic  and  absorbed,  the  exposed  sternum  forming  a  part  of  the 
cavity  of  the  aneurysm.  The  bone  also  disappeared  under  the 
pressure  and  pulsation  of  the  aneurysm,  the  anterior  wall  of  which 
was  then  formed  by  the  periosteum  and  fibrous  tissue.  This  also 
gave  way  allowing  the  aneurysm  to  perforate  into  the  subcutaneous 
tissue,  forming  a  large  haemorrhage  in  which  the  blood  coagulated. 


120  PATHOLOGY 

The  new  cavity  gradually  grew  by  the  continued  haemorrhage,  the 
skin  became  perforated,  allowing  external  haemorrhage,  and  there 
was  also  haemorrhagic  infiltration  into  the  surrounding  tissue. 


ANEURYSM  OF  THE  ABDOMINAL  AORTA  WITH  EROSION  OF 
VERTEBRJS 

Anatomical  Diagnoses.    Arterio-sclerosis;   Aneurysm  of  abdominal 
aorta  with  occlusion  of  abdominal  arteries. 

(Only  that  portion  of  the  autopsy  protocol  relating  to  the  aneurysm 
is  quoted.) 

Death  was  due  to  infection  following  operation  for  appendicitis. 

Male,  white,  age  thirty-nine  years.  Body  that  of  a  well-nourished, 
well-developed  and  powerfully  built,  tall  man,  182  cm.  in  length.  Rigor 
mortis  complete.  Post  mortem  lividity  marked.  After  removal  of 
intestines  a  tumor  mass  is  found  lying  upon  the  vertebrae  and  bordered 
on  each  side  by  the  crura  of  the  diaphragm. 

Heart,  weight,  350  grams,  myocardium  firm,  valves  and  endocardium 
normal.  Coronary  arteries  show  an  occasional  soft  yellow  patch.  The 
beginning  of  the  aorta  is  thickly  studded  with  small  elevated,  white  and 
yellow  areas  without  calcification. 

The  aorta  is  continuous  above  and  below  with  the  tumor  mass  in  the 
abdomen  which  lies  over  the  lower  dorsal  and  upper  two  lumbar  vertebrae 
and  is  included  between  the  crura  of  the  diaphragm.  The  aorta  is 
removed  by  stripping  from  the  vertebras  as  far  as  possible  from  above  and 
below  until  it  became  firmly  adherent  to  the  vertebrae.  These  vertebrae 
were  then  sawn  through  and  the  aorta  opened  from  behind  by  means  of 
the  incision  through  the  vertebrae.  Over  the  twelfth  dorsal,  first  and 
second  lumbar  vertebrae  is  an  aneurysm  sac  14  cm.  long  and  13  cm.  in 
its  greatest  diameter.  The  first  and  second  lumbar  vertebrae  are  exca- 
vated for  a  depth  of  2-3  cm.  The  articular  fibro-cartilages  are  only 
slightly  eroded  and  project  between  the  eroded  vertebrae.  The  cavities 
in  these  two  vertebrae  are  filled  with  firm  grayish-red  clot.  The  general 
shape  of  the  sac  is  fusiform,  and  at  the  level  of  the  first  lumbar  vertebra 
a  second  sac  3  cm.  deep  and  4  cm.  in  diameter  is  given  off  from  the 
anterior  wall  of  the  main  aneurysm.  The  main  aneurysm  contains  but 
a  small  amount  of  fibrin  most  of  which  lies  against  the  vertebras  where 
the  eroded  bone  forms  the  posterior  wall.  The  small  sac  contains  fresh 
dark  red  clot.  The  aorta  above  and  below  the  aneurysm  and  the  an- 
eurysm wall  is  thickly  covered  with  corrugated,  elevated  white  and  yellow, 
patches  which  are  more  numerous  above  the  aneurysm  than  below. 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     12 1 

There  is  no  calcification.  The  common  iliac  arteries  are  very  slightly 
sclerosed,  the  left  has  one  patch  only,  the  right  several  patches.  The 
inferior  mesentery  and  renal  arteries  are  patent.  At  the  orifices  of  the 
left  renal  artery  is  a  conical  bulging  of  the  aneurysm  wall  about  i  cm.  in 
diameter  and  depth.  Where  the  phrenic  and  cceliac  axis  and  superior 
mesenteric  arteries  are  given  off  from  the  aneurysm  they  are  occluded 
by  firm,  friable,  grayish  clots. 

REMARKS.  The  aneurysm  is  given  off  from  the  posterior  portion 
of  the  abdominal  aorta.  In  this  case,  the  bodies  of  these  vertebrae 
are  eroded  as  was  the  sternum  in  the  preceding  case.  The  inter- 
vertebral  fibrocartilages  are  extremely  resistant  to  the  process  and 
stand  out  between  the  bodies  of  the  eroded  vertebrae.  The  aneu- 
rysm is  evidently  fusiform,  the  whole  wall  of  the  artery  being  in- 
volved in  it.  Although  the  wall  of  the  aneurysm  is  often  irregular, 
it  is  rather  uncommon  to  have  a  secondary  aneurysm  formed  in  the 
aneurysmal  wall  as  in  this  case.  The  aorta  shows  an  extensive 
arterio-sclerosis  without  calcification,  in  type  resembling  the  syphil- 
itic form,  but  does  not  resemble  this  in  the  extent  of  the  area 
involved.  Notice  that  there  is  no  heart  hypertrophy. 

A  CASE  OF  SACULAR  ANEURYSM  OF  THE  ARCH  OF  THE  AORTA 

Anatomical  Diagnoses.  Aneurysm  of  the  arch  of  the  aorta;  Erosion 
of  the  sternum;  Hydrothorax;  Obliteration  of  lumen  of  appendix 
with  cystic  dilatation;  Chronic  pleurisy;  Compression  atelec- 
tasis  of  lung;  Bronchopneumonia;  Arterio-sclerosis  of  aorta ; 
Bronchitis. 

Negro,  male,  age  sixty  years.  The  body  large,  strongly  built,  greatly 
emaciated,  the  abdomen  retracted.  Subcutaneous  fat  small  in  amount 
and  yellow.  Muscles  wasted,  thin  and  red.  All  tissues  remarkably  dry. 

The  appendix  long,  its  tip  attached  to  rectum.  The  distal  one  half 
of  the  appendix  is  dilated,  the  proximal  contracted.  It  is  surrounded 
by  adhesions.  On  section  there  is  complete  obliteration  of  the  lumen 
up  to  the  dilated  half.  The  average  diameter  of  the  dilated  distal  half 
is  2  cm.  This  is  filled  with  clear,  mucoid  material,  its  mucous  membrane 
thrown  into  folds. 

The  costal  cartilages  are  ossified.  The  sternum  is  thin,  the  bone 
porous,  easily  crushed.  The  entire  anterior  mediastinum  is  filled  with 
a  large  tumor  mass  extending  to  the  left  side.  This  mass  is  adherent  to 
the  sternum  and  which  is  eroded  over  the  surface  of  contact.  With  the 


122  PATHOLOGY 

exception  of  the  condition  in  the  vermiform  appendix,  no  lesions  are 
found  in  the  abdominal  organs  save  a  well-marked  chronic  passive 
congestion. 

Pleura.  Left  side  of  the  chest  is  filled  with  bloody  fluid.  The  right 
is  dry.  The  left  lung  is  retracted  and  adherent  to  the  chest  wall  by 
dense,  long  drawn  out  adhesions.  Where  these  adhesions  are  attached 
to  the  lung,  this  projects  in  long  papillary  masses.  The  lung  is  adherent 
to  the  pericardium,  to  the  tumor  mass  and  to  the  vertebra,  and  so 
reduced  in  size  that  the  entire  organ  forms  a  mass  not  much  larger  than 
the  closed  fist.  The  entire  pleural  surface  is  covered  with  a  thick,  red 
granular  membrane.  On  section  the  lung  is  completely  solid  with  a 
creamy  exudation  exuding  from  the  bronchi  and  from  the  compressed 
lung  tissue.  On  section  of  the  right  lung  an  abundance  of  muco  pus  can 
be  squeezed  from  the  bronchi.  Smears  from  this  pus  show  a  variety  of 
organisms,  diplococci  in  pairs  conforming  morphologically  to  pneumo- 
cocci  predominating. 

The  pericardial  cavity  obliterated  by  firm  adhesions. 

The  heart  is  somewhat  dislocated  downward  and  to  the  left.  It  is 
of  normal  size,  myocardium  and  valves  normal. 

The  tumor  mass  in  the  anterior  mediastinum  is  formed  by  an  aneurysm 
springing  from  the  antero-lateral  side  of  the  ascending  aorta  just  before 
the  origin  of  the  innominate.  The  superior  inferior  diameter  of  the 
aneurysm  is  15  cm.,  the  antero-posterior  is  13  cm.  It  extends  more  on 
the  left  side  of  the  median  line  and  has  sharply  compressed  the  vessels 
at  the  root  of  the  left  lung.  The  opening  into  the  aneurysm  is  oval, 
the  average  diameter  of  this  is  4  cm.  The  edge  of  the  opening  is  per- 
fectly smooth.  The  aneurysm  is  filled  with  dense  laminated  fibrin  and 
fresher  clots. 

The  ascending,  transverse  and  thoracic  aorta  is  thickened,  the  cica- 
tricial  tissue  showing  nonelevated  white  opacities  and  small  partially 
elevated  plaques.  There  is  but  little  arterio-sclerosis  in  the  remaining 
arteries. 

REMARKS.  This  is  a  good  example  of  the  sacular  aneurysm. 
There  is  a  general  condition  of  arterio-sclerosis,  but  the  condition 
especially  favoring  the  aneurysm  formation  existed  at  a  circum- 
scribed area  which  gave  way.  The  large  tumor  mass  which  was  so 
farmed  has  pressed  against  the  sternum,  producing  a  slight  erosion 
of  the  bone.  The  very  extensive  hydrothorax  on  the  left  side  is 
probably  to  some  extent  due  to  the  compression  of  the  veins  at  the 
root  of  the  lung  by  the  aneurysmal  tumor.  The  lung  was  adherent 
to  the  pleura  by  dense  adhesions  before  the  formation  of  fluid  in 


THE  PATHOLOGICAL  PHYSIOLOGY  OF  THE  CIRCULATION     123 

the  pleural  cavity  began.  These  adhesions  have  stretched  to  a 
large  extent,  but  have  drawn  out  the  tissue  of  the  lung  in  masses 
at  the  point  of  attachment.  The  fibrinous  exudation  on  the  surface 
of  the  lung  has  become  completely  organized  with  the  formation 
of  a  red  granular  membrane.  The  lung  has  also  been  the  seat  of  a 
chronic  infection  with  probably  an  acute  following.  The  condition 
of  the  appendix  is  interesting.  There  has  been  here  a  primary  acute 
appendicitis  with  destruction  of  the  mucous  membrane  and  oblitera- 
tion of  half  of  the  lumen.  In  the  distal  half  there  has  been  a 
continuous  secretion  of  mucus  from  the  mucous  membrane  which 
has  accumulated,  forming  a  cyst  of  the  appendix.  Cysts  of  the 
appendix  so  produced  may  attain  a  considerable  size,  even  up  to 
6  or  8  cm.  in  diameter. 


123  a 


123  b 


123  C 


123  d 


123  e 


123  f 


123  h 


1231 


123  J 


123  m 


123  n 


1230 


123  P 


123  q 


123 


123  s 


123  u 


123  V 


123  x 


GROWTH,  HYPERTROPHY,  HYPERPLASIA,  REGENERATION 

New  formation  of  cells  and  tissue  is,  as  we  have  seen,  one  of  the 
most  constant  phenomena  in  inflammation  and  it  is  by  means  of 
this  that  the  injury  to  the  tissue  is  repaired.  The  new  formation 
of  cells  takes  place  by  indirect  or  mitotic  nuclear  division.  The 
complicated  process  of  this  division  makes  it  possible  for  the  new 
nuclei  to  have  parts  of  all  the  chromatin  of  the  old  nucleus.  Direct 
division  of  nuclei  may  take  place  in  degenerated  cells  of  the  tissue, 
but  save  in  tumor  cells,  it  does  not  lead  to  new  cell  formation. 
After  the  application  of  a  caustic  to  the  centre  of  the  cornea  such 
direct  nuclear  division  without  new  formation  of  cells  and  without 
cell  growth  may  be  seen  in  the  swollen  and  degenerated  cells  around 
the  site  of  injury,  and  not  infrequently  in  degenerated  epithelial 
cells,  groups  of  nuclei  may  be  seen.  A  similar  multiplication  of 
sarcolemma  nuclei  attends  many  of  the  forms  of  muscle  degenera- 
tion. In  this  process  there  is  no  increase  of  chromatin  preceding 
the  division  and  the  new  nuclei  have  but  little  and  irregularly 
distributed  chromatin. 

Most  tissues  in  the  body  possess  a  capacity  for  growth  which 
differs  in  degree  in  different  tissues.  In  those  tissues  in  which 
growth  constantly  takes  place,  as  the  blood  and  cutaneous  epi- 
thelium, the  growth  capacity  is  greatest.  It  can  be  active  also  in 
those  tissues  in  which  there  is  the  least  degree  of  cell  differentiation 
as  in  the  endothelium  and  the  connective  tissues.  It  has  been 
shown  recently  that  growth  of  cells  will  also  take  place  outside  of 
the  body  when  the  environment  is  suitable. 

One  of  the  causes  assigned  for  new  cell  formation  after  injury 
is  that,  by  the  disturbance  of  tissue  relations  and  equilibrium,  the 
restraint  to  growth  which  the  cells  mutually  exert  upon  each  other 
is  removed.  This  theory  assumes  that  growth  is  not  due  to  a 
stimulation  of  the  formative  capacity  of  cells,  but  that  the  forma- 
tive capacity,  always  active,  is  held  in  check  by  a  restraining  influ- 
ence of  adjoining  cells.  There  is  no  doubt  that  the  surest  way  to 
excite  cell  proliferation  is  the  production  of  loss  of  substance.  The 
growth  takes  place  not  only  from  the  cells  in  the  immediate  vicinity 

124 


of  the  loss,  but  in  cells  at  a  distance,  the  most  striking  instance  of 
this  being  the  new  formation  of  the  leucocytes  in  inflammations. 
This  may  be  thought  of  as  similar  in  character  to  the  tissue  growth 
around  an  injury.  The  withdrawal  of  the  leucocytes  from  the 
blood,  the  hypoleucocytosis,  destroys  the  blood  cell  equilibrium,  i.e. 
the  relative  proportions  in  the  numbers  of  leucocytes,  which  is 
restored  by  proliferation  in  the  blood  tissue  in  the  same  way  that 
loss  of  epithelium  or  connective  tissue  cells  is  made  good  by  pro- 
liferation of  adjoining  cells.  Such  a  regulating  mechanism  of 
growth  must  be  more  than  the  mere  physical  contact  of  cells,  and 
its  action  must  be  by  chemical  agencies.  It  is  possible  to  think 
that  each  tissue  in  the  body  may  produce  substances  which  stimu- 
late or  restrain  the  formative  capacity  of  cells  and  that  the  normal 
equilibrium  of  the  tissues  is  due  to  the  interaction  of  such  sub- 
stances. That  chemical  substances  of  the  nature  of  hormones  can 
excite  growth  in  organs  is  evident  both  in  physiology  and  pathology, 
instances  being  the  growth  of  the  mammae  in  pregnancy  and  the 
abnormal  growth  of  the  extremities  in  pathological  conditions  of 
the  hypophysis.  By  the  injection  of  Scharlach  R.  into  the  sub- 
cutaneous tissues,  an  active  growth  of  the  adjacent  epithelial  cells 
can  be  produced.  In  case  of  the  blood  formation  chemotactic 
substances  from  the  inflamed  area  may  enter  into  the  blood  and 
in  consequence  of  their  action  the  leucocytes  already  formed  in  the 
marrow  enter  into  the  blood  producing  an  actual  loss  of  substance 
in  the  marrow  tissue.  The  examination  of  the  marrow  shows  that 
the  first  change  following  hypoleucocytosis  is  the  withdrawal  of 
the  stored  leucocytes  of  the  marrow  and  this  is  followed  by  pro- 
liferation. In  the  course  of  many  of  the  infectious  diseases  new 
formation  of  cells  takes  place,  not  only  in  relation  to  the  local 
injury  produced  by  the  bacteria,  but  remotely,  due  to  the  action 
of  toxic  substances  brought  to  the  tissues  by  the  blood.  One  of 
the  most  common  conditions  in  infections  is  the  production  of 
phagocytic  cells  in  the  liver  by  proliferation  of  the  endothelium  of 
the  capillaries.  The  action  of  phagocytes  in  certain  cases  seems  to 
be  a  mode  of  restoring  the  cell  equilibrium  when  in  an  area  there 
is  an  excess  of  cells  of  the  lymphoid  type. 

HYPERTROPHY  AND  HYPERFLASIA.  By  hypertrophy  is  under- 
stood increased  size  of  an  organ  due  to  increased  size  and  increased 
functional  capacity  of  its  essential  elements,  whereas  by  the  term 


126  PATHOLOGY 

hyperplasia  a  numerical  increase  is  indicated.  No  sharp  line  can 
be  drawn  between  these  processes;  in  certain  organs  the  increase 
in  size  of  the  elements,  in  others  the  numerical  increase,  is  the  domi- 
nant factor.  Increase  in  size  of  an  organ  is  not  identical  with 
hypertrophy,  but  may  accompany  atrophy,  as  is  seen  in  degen- 
erated muscle  in  which  there  often  is  a  large  formation  of  interstitial 
fat,  and  in  emphysema  of  the  lungs  in  which  the  air  cells  are  dilated 
and  lung  tissue  reduced  in  amount.  The  best  examples  of  hyper- 
trophy are  seen  in  the  increased  thickness  of  the  muscular  walls  of 
hollow  organs  when  there  is  obstruction  in  their  outlet.  The  wall 
of  the  left  ventricle  may  increase  to  more  than  double  its  normal 
thickness  when  there  is  obstruction  at  the  aortic  outlet  and  the  wall 
of  the  bladder  greatly  hypertrophies  in  cases  of  stricture  of  the 
urethra.  Such  hypertrophy  is  similar  in  its  general  character  to 
the  muscle  hypertrophy  produced  by  exercise.  There  is  a  close 
relation  between  the  functional,  nutritive  and  formative  capacity 
of  cells.  The  increased  exercise  of  function  brings  about  increased 
blood  supply  and  more  active  nutritive  changes,  and  under  such 
conditions  the  formative  activity  may  also  become  stimulated. 
Whether  the  formative  activity  leads  to  hypertrophy  or  to  hyper- 
plasia depends  upon  the  nature  of  the  tissue.  It  is  doubtful  if 
there  is  any  increase  in  the  number  of  fibres  in  the  hypertrophy  of 
the  voluntary  and  cardiac  muscle.  In  the  hypertrophy  of  the 
muscular  coats  of  the  intestine  above  a  stricture  there  is  numerical 
increase  with  the  enlargement;  in  the  hypertrophy  of  the  uterus 
during  pregnancy  there  is  great  enlargement  of  fibres  without  in- 
crease in  number.  In  glandular  organs  enlargement  of  the  glands 
cells  takes  place  to  but  a  limited  extent.  Hypertrophy  of  an 
organ  will  not  takes  place  when,  in  consequence  of  disease,  the 
conditions  for  increased  nutrition  are  not  favorable.  The  hyper- 
trophied  organ  is  not  a  normal  organ.  The  range  of  conditions  to 
which  the  normal  organ  can  adapt  itself  by  an  increase  of  function 
is  diminished,  and  the  capacity  for  growth  diminishes  with  its 
exercise.  If  the  demands  made  upon  the  hypertrophied  heart 
continue  to  increase,  a  time  comes  when  the  organ  seems  incapable 
of  further  hypertrophy.  In  addition  to  increased  size  and  number 
of  elements  there  usually  are  other  morphological  changes  shown 
by  a  relative  increase  in  connective  tissue  and  in  abnormal  relation 
between  nucleus  and  cytoplasm. 


GROWTH,  HYPERTROPHY,  HYPERPLASIA,  REGENERATION    127 

In  the  case  of  paired  organs  removal  of  one  will,  in  some  cases, 
lead  to  hypertrophy  of  the  other,  —  compensatory  hypertrophy. 
When  one  kidney  is  removed  the  other  will  enlarge,  and  the  single 
organ  can  then  perform  the  work  of  the  two.  In  this  enlargement 
the  tubules  become  larger  and  longer  than  normal;  there  is  an 
increased  formation  of  epithelial  cells,  an  increase  in  the  size  of  the 
glomeruli,  but  no  new  formation  of  tubules  or  glomeruli.  In  the 
case  of  organs  more  or  less  closely  related,  hypertrophy  of  one  may 
take  place  on  the  removal  of  the  others.  Thus,  after  removal  of 
the  thyroid  the  hypophysis  may  hypertrophy.  In  the  case  of 
paired  organs  in  which  there  is  not  constant  but  periodic  function, 
such  compensating  hypertrophy  does  not  take  place  or  takes  place 
to  but  a  limited  extent.  Nor  does  this  hypertrophy  take  place  in 
the  lung.  The  removal  of  one  lung  may  produce  an  excessive 
enlargement  of  the  other,  but  the  condition  is  rather  that  of  em- 
physema rather  than  a  true  hypertrophy.  Compensatory  hyper- 
trophy takes  place  readily  in  the  related  tissues  of  the  lymphatic 
apparatus. 

REGENERATION.  By  this  is  understood  a  new  formation  of  tissue 
to  take  the  place  of  a  loss,  the  new  tissue  having  the  same  structure 
and  function  as  that  which  was  lost.  To  what  extent  cell  destruc- 
tion followed  by  regeneration  takes  place  in  the  normal  tissues  is 
uncertain.  In  the  covering  epithelium  both  of  the  exterior  and 
interior  surfaces  there  is  constant  cell  loss  which  is  made  good  by 
new  formation.  As  evidence  of  this,  nuclear  figures  always  are 
found  in  the  malpighian  layer  of  the  skin  and  in  the  intestine;  in 
the  latter,  the  new  cell  formation  takes  place  almost  exclusively  in 
the  crypts.  In  the  blood  there  is  constant  cell  destruction  and 
regeneration  shown  by  nuclear  figures  in  the  marrow  and  lymph 
nodes.  In  the  normal  glandular  organs  nuclear  figures  are  ex- 
tremely uncommon  except  in  conditions  of  great  functional  activity. 

There  are  certain  general  laws  which  seem  to  apply  to  regenera- 
tion. The  less  complicated  the  structure  of  an  organism,  the 
greater  is  the  power  of  regeneration.  It  is  most  perfect  in  the 
unicellular  organisms  and  decreases  with -complexity  of  organiza- 
tion. In  the  single  organs  regeneration  is  less  perfect  the  greater 
the  functional  differentiation  of  cells  and  the  greater  the  com- 
plexity of  architectural  structure.  Regeneration  may  be  active  in 
the  single  cells  of  a  tissue,  but  in  the  new  growth  the  perfect  inter- 


128  PATHOLOGY 

relations  of  tissue  may  not  be  restored  (repair).     The  younger  the 
animal  the  greater  the  power  of  regeneration. 

In  the  central  nervous  system  there  is  no  power  of  regeneration. 
There  is  not  only  a  greater  degree  of  functional  differentiation  of 
the  ganglion  cells  than  in  other  cells,  but  the  architectural  structure 
of  the  tissue  is  so  complicated  that  a  new  formation  of  tissue  with 
the  re-establishment  of  the  intricate  relations  of  cells  and  fibrils 
would  seem  impossible.  Although  there  is  no  regeneration  in 
the  central  nervous  system,  there  is  great  regenerative  power  in 
the  peripheral  nerves.  After  section  of  a  nerve,  the  entire  peripheral 
portion  degenerates  and  there  is  degeneration  of  the  central  end 
up  to  the  nodes  of  Ranvier.  In  the  process  of  regeneration  the 
axis  cylinders  grow  out  from  the  central  end  and  attain  a  peripheral 
distribution,  this  taking  place  more  readily  if  they  can  gain  accept 
to  the  degenerated  peripheral  end.  Only  the  axis  cylinders  grow 
out  in  this  way,  the  sheath  of  Schwann  being  formed  peripherally. 

In  the  skin,  regeneration  of  the  covering  epithelium  quickly 
takes  place,  but  when  there  is  destruction  both  of  skin  and  papillary 
layer,  the  papillae  are  not  at  all  or  are  imperfectly  regenerated.  If 
in  smallpox  the  destruction  of  tissue  involves  the  papillary  layer,  a 
smooth  scar  results.  When  the  skin  glands  and  other  epidermic 
structures  are  destroyed  they  are  not  regenerated.  In  the  scar 
resulting  from  a  healed  ulcer  there  are  neither  hairs,  sebaceous 
glands,  nor  sweat  glands.  Much  the  same  thing  is  true  of  the 
alimentary  canal.  There  is  great  power  of  regeneration  of  a  loss 
confined  to  the  epithelium,  but  new  formation  of  villi  does  not  take 
place  and  the  newly  formed  simple  glands  are  very  imperfect. 
The  healed  typhoid  ulcer  shows  a  smooth  surface  covered  with 
epithelium  but  without  villi  and  with  the  glands  represented  by 
a  few  irregularly  distributed  short  tubules. 

Such  complicated  glandular  structures  as  the  mammary  and 
salivary  glands,  in  which  there  is  epithelial  differentiation  into 
secreting  epithelium  and  ducts,  have  slight  capacity  for  regenera- 
tion. The  new  formation  of  epithelial  structures  proceeds  rather 
from  the  less  perfectly  differentiated  ducts  than  from  the  secreting 
cells  of  the  alveoli,  and  the  new  tissue  is  imperfect.  In  the  liver, 
on  the  other  hand,  there  is  greater  regenerative  capacity  than  in 
any  other  organ  of  the  body.  It  is  possible  to  produce  by  chloro- 
form poisoning  necrosis  of  cells  in  the  centre  of  the  lobule  extending 


GROWTH,  HYPERTROPHY,  HYPERPLASIA,  REGENERATION    129 

half  way  to  the  periphery,  and  in  four  days  after  this  to  have  the 
lost  tissue  so  completely  and  perfectly  reproduced  that  there  is  no 
microscopic  evidence  of  the  former  destruction.  The  liver,  how- 
ever, in  the  relations  of  cells  and  vessels  is  one  of  the  simplest 
epithelial  structures  in  the  body.  After  chloroform  necrosis  the 
cells  around  the  injury  multiply  rapidly  as  is  shown  by  numerous 
mitotic  figures  and  the  new  cells  extend  along  the  capillary  frame- 
work which  remains  intact.  Necrosis  of  single  cells  often  occurs 
and  may  be  produced  experimentally,  and  new  cells  are  quickly 
formed.  Where  there  is  more  extensive  destruction,  involving  also 
the  architecture  of  the  organ,  regeneration  takes  place  both  from 
the  liver  cells  and  by  growth  of  the  bile  ducts  with  differentiation 
of  their  cells  into  liver  cells.  Under  such  conditions  the  newly 
formed  tissue  is  not  a  complete  reproduction  of  the  old,  the  lobules 
being  larger,  less  perfect  in  structure,  and  these  is  increase  in  the 
amount  of  connective  tissue. 

In  the  kidney  there  is  not  complete  regeneration  of  lost  tissue; 
neither  new  tubules  nor  glomeruli  are  formed.  The  loss  of  single 
epithelial  cells  is  made  good  by  proliferation  of  the  adjoining  cells, 
if  the  integrity  of  the  tubule  as  a  structure  is  preserved.  The 
glomeruli  and  tubules  can  undergo  compensatory  hypertrophy  in 
the  single  organ,  just  as  in  the  remaining  kidney  after  removal  of 
its  fellow.  In  kidneys  in  which  there  has  been  considerable  de- 
struction, glomeruli  much  larger  than  normal  may  be  found  and 
single  tubules  may  become  enlarged  and  elongated.  In  the  ovary 
and  testicle  there  is  no  power  of  regeneration  of  the  sexual  cells. 
Any  growth  which  results  comes  from  the  interstitial  tissue. 

Regeneration  of  striated  muscle  is  very  imperfect.  There  is  no 
complete  new  formation,  but  there  may  be  an  imperfect  growth 
from  the  severed  ends  of  fibres.  After  degeneration  of  muscle, 
large  cells  may  be  seen  within  the  sarcolemma  which  have  been 
considered  sarcoblasts.  It  is  more  probable,  however,  that  these 
are  merely  phagocytic  cells  and  concerned,  not  with  muscle  forma- 
tion, but  with  the  removal  of  degenerated  tissue. 

The  regeneration  of  bone  is  complex;  it  does  not  take  place  from 
the  old  bone  but  by  means  of  the  formation  of  a  cellular  tissue  from 
the  periosteum,  and  to  a  less  extent  from  the  endosteum,  in  which 
bone  developes  as  in  the  embryo.  In  this  germinal  tissue  a  network 
of  bone  is  formed  by  means  of  a  homogeneous  intercellular  sub- 


130  PATHOLOGY 

stance  which  at  first  is  imperfectly  calcified  and  in  which  the  form- 
ing cells  become  the  future  bone  corpuscles.  In  this  tissue,  islands 
of  cartilage  are  often  formed  by  the  production  of  a  hyalin  inter- 
cellular substance  which  contains  chondrin,  and  from  this  tissue 
bone  formation  can  proceed.  New  vessels  growing  out  from  the 
old  are  abundant  and  about  them  myeloid  tissue  may  appear. 
The  new  formation  of  bone  is  very  abundant;  in  a  fracture  it 
extends  to  a  considerable  distance  beyond  the  fractured  ends  and 
serves  as  a  temporary  splint.  It  is  gradually  absorbed  by  the 
phagocytic  osteoclasts  and  a  more  compact  bone  replaces  it.  No 
regeneration  in  cartilage  takes  place  by  growth  of  the  cartilage 
cells.  As  in  bone,  a  germinal  tissue  is  formed  from  the  perichon- 
drium  within  which  new  cartilage  is  produced. 

METAPLASIA.  This  is  the  production  of  specialized  tissue  from 
cells  which  normally  produce  tissue  of  another  sort.  In  regenera- 
tion it  was  seen  that  the  new  formation  of  tissue  takes  place  from 
tissue  of  a  similar  character.  The  most  striking  example  of  meta- 
plasia is  the  formation  of  bone  in  parts  which  normally  do  not  con- 
tain bone.  Bone  may  be  formed  under  pathological  conditions  in 
the  choroid  of  the  eye,  in  the  lungs,  in  the  heart  valves,  arterial 
walls,  in  the  kidney,  and  in  other  places.  In  such  bone,  marrow 
spaces  and  marrow  may  be  found.  Cartilage  also  may  form  in 
places  where  it  is  not  normally  present.  The  various  epithelia  of 
the  body  also  afford  instances  of  metaplasia.  Chronic  ulcers  of 
the  trachea  may  heal  by  the  formation  of  squamous  epithelium 
on  the  surface.  If  the  inner  surface  of  the  bladder  or  of  the  uterus 
be  exposed  to  an  irritating  environment,  the  new  epithelium  takes 
the  character  of  epidermis;  in  chronic  inflammation  of  the  gall 
bladder  the  same  is  true.  Cartilage  may  disappear  in  an  im- 
mobilized joint  and  be  replaced  by  connective  tissue.  In  none  of 
these  cases  is  there  a  conversion  of  one  tissue  into  another,  the 
metaplastic  tissue  being  newly  formed.  There  is  a  limited  range  only 
of  such  metaplasia;  it  occurs  in  tissues  nearly  related  and  of  the 
same  embryonic  origin,  and  does  not  occur  in  tissues  of  complex 
structure.  One  epiblastic  or  hypoblastic  tissue  can  be  converted 
into  another  epiblastic  or  hypoblastic  tissue,  but  mesoblastic  tissue 
is  not  converted  into  epiblastic  or  hypoblastic  and  vice  versa. 


130  a 


130  L 


130  c 


130  d 


TUMORS 

A  tumor  is  a  new  formation  of  tissue  which  in  growth,  in  struc- 
ture, and  relations  departs  to  a  greater  or  less  degree  from  the 
normal  type  of  the  tissue  to  which  it  is  related  in  structure  or  origin, 
and  from  all  other  forms  of  pathological  growth.  It  is  an  autono- 
mous structure  growing  in  the  body  as  a  parasite,  and  its  growth 
capacity  is  unlimited.  The  human  body  is  an  organism,  and  the 
various  tissues  and  organs  of  the  body  are  not  independent  entities 
but  show  an  intimate  relation  of  all  parts  with  the  whole.  There 
is  every  reason  to  believe  that  this  interrelation  and  coordination, 
this  control  and  direction  of  all  the  activities  of  the  tissues,  is,  in 
great  part  at  least,  effected  by  means  of  substances  called  hormones 
or  chemical  messengers  which  are  produced  as  one  form  of  internal 
secretion  in  the  ductless  glands  and  in  other  organs  of  the  body. 
The  capacity  of  the  tissues  for  growth  varies  with  the  tissue  and 
with  age  and  it  may  be  stimulated  in  various  ways.  The  growth, 
however,  in  its  main  characteristics  is  purposeful  and  subordinated 
to  the  organism.  A  tumor  cannot  be  considered  as  an  organ  of  the 
body,  its  activities  not  being  coordinated  with  the  organism.  It 
is  a  part  of  the  body,  but  it  is  rather  to  be  considered  as  a  wild  and 
lawless  guest  not  influenced  by,  or  conforming  with,  the  regulations 
of  the  household.  In  the  capacity  for  growth  the  cells  of  tumors 
can  be  compared  rather  with  plant  than  with  animal  cells.  The 
rapidity  of  growth  varies,  certain .  tumors  for  years  showing  but 
little  increase  in  size,  others  being  seen  to  increase  almost  from  day 
to  day.  The  growth  is  often  intermittent,  periods  of  quiescence 
alternating  with  periods  of  activity.  The  nutrition  and  growth  of 
a  tumor  is  but  little  influenced  by  the  condition  of  nutrition  of  the 
host.  Very  rapid  growth  may  be  seen  in  conditions  of  extreme 
malnutrition  and  emaciation  of  the  host. 

IN  SIZE,  a  tumor  may  be  microscopic,  or  it  may  exceed  the  weight 
of  the  individual  who  bears  it.  The  limitations  to  its  growth  are 
external  and  not  internal.  There  is  no  distinctive  color  to  a  tumor. 
Certain  tumors  have  color  which  depends  upon  the  presence  of 


132  PATHOLOGY 

definite  pigments  produced  by  the  tumor  cells,  such  as  the  brown 
or  black  pigment  of  the  melanotic  sarcoma  and  the  green  pigment 
of  the  chloroma.  There  also  may  be  considerable  amounts  of 
haematogenous  pigment,  the  remains  of  haemorrhages  which  have 
taken  place.  Usually  tumors  have  a  gray  color  modified  by  their 
varying  vascularity,  with  the  appearance  also  of  whitish  and  more 
opaque  areas  due  to  variations  in  the  amount  of  fat  in  the  cells. 
There  is  every  variation  in  consistency,  from  that  of  a  tissue  so 
soft  that  it  can  easily  be  pressed  through  the  fingers  to  a  con- 
sistence of  stony  hardness.  The  shape  of  a  tumor  depends  upon 
its  nature,  manner  of  growth,  and  situation.  When  it  arises  near 
a  surface  it  may  project  from  a  pedunculated  attachment;  both  in 
this  situation  and  within  the  tissues  it  may  be  round  or  lobulated 
or  irregular,  the  shape  being  influenced  by  the  varying  opposition 
of  surrounding  tissues  to  its  growth. 

STRUCTURE.  Like  other  tissues,  tumors  are  composed  of  cells, 
intercellular  substances,  blood  vessels  lymphatics  and  rarely 
nerves.  No  general  description  can  be  given  of  the  cells  of  tumors, 
there  being  too  much  variation  in  relative  numbers,  in  size,  struc- 
ture and  relation  between  nucleus  and  cytoplasm.  The  energies 
of  the  cells  in  tumors  are  almost  exclusively  directed  towards 
growth  and  nutrition  and  there  is  some  correspondence  between 
the  growth  of  tumor  cells  and  rapid  cell  growth  in  other  conditions. 
As  in  normal  tissue,  growth  takes  place  by  cell  multiplication  which 
usually  is  preceded  by  mitosis.  Direct  nuclear  division,  division 
by  nuclear  budding  and  by  complicated  multiple  mitoses,  also 
occurs.  From  continued  growth  without  division  enormous  cells 
containing  large  and  irregular  nuclear  masses  may  be  seen.  In 
certain  tumors  the  presence  of  giant  cells  with  multiple  nuclei 
form  so  distinguishing  a  feature  as  to  affect  the  nomenclature 
(giant  cell  sarcoma).  Tumor  cells  very  frequently  contain  fat. 
Glycogen  may  be  found  within  them,  as  well  as  hyalin  masses 
which  give  no  definite  chemical  reaction  and  which  are  often  en- 
closed in  vacuoles.  Chromatin  granules  cast  off  from  the  nucleus, 
assuming  various  forms  and  often  associated  with  the  hyalin  sub- 
stances, are  often  present.  In  certain  tumors  the  cells  seem  to 
be  amoeboid;  on  the  warm  stage  slow  amoeboid  movements  have 
been  seen,  and  in  rapidly  fixed  tissues  we  may  find  cells  in  shapes 
and  positions  which  we  are  accustomed  to  associate  with  amoeboid 


TUMORS  133 

activity.      Phagocytosis   may    occur,    but   is   not    a    prominent 
characteristic. 

THE  INTERCELLULAR  SUBSTANCES  have  a  varying  relation.  In 
certain  cases  they  are  produced  by  the  tumor  cells  and  form  an 
integral  part  of  the  tumor;  in  other  cases,  especially  in  the  epi- 
thelial tumors,  there  is  a  definite  separation  between  the  actively 
growing  cells  which  give  the  tumor  its  characteristics  and  a  con- 
nective tissue  stroma  which  bears  the  blood  vessels  and  forms  a 
framework  supporting  the  cell  masses.  Such  a  stroma  is  a  growth 
coming  from  the  host,  secondary  to  and  dependent  upon  the  growth 
of  the  epithelium,  comparable  to  the  connective  tissue  growth  in 
developing  organs  of  the  embryo. 

THE  BLOOD  SUPPLY  of  tumors  varies  with  the  character  of  the 
tissue  and  the  rapidity  of  growth.  Blood  vessels  are  abundant  in 
the  rapidly  growing  tumors,  the  reverse  in  the  slow.  They  grow 
with  the  tumor  and  come  from  the  adjacent  blood  vessels  of  the 
host.  They  may  enter  the  tumor  from  a  single  point,  but  usually, 
as  the  tumor  enlarges,  new  vascular  connections  are  formed.  The 
vessels  of  the  host  which  provide  the  nutrition  of  the  tumor  enlarge 
with  its  growth.  The  blood  vessels  are  irregular,  and  there  is  not 
always  the  definite  differentiation  into  arteries,  capillaries  and 
veins  as  in  the  normal  tissues.  The  vessels  often  have  the  char- 
acter of  large  thin- walled  capillaries  with  an  irregular  lumen;  often 
they  are  mere  channels  with  only  a  layer  of  endothelial  cells  sepa- 
rating the  blood  from  the  tumor  cells.  In  such  a  condition  dis- 
turbances in  the  circulation  from  the  pressure  of  the  growing  tissue 
on  the  vessels  are  common,  with  resulting  necrosis,  infarction  or 
simple  haemorrhage.  Very  little  is  known  regarding  lymphatics  in 
tumors.  Spaces  lined  with  endothelium  are  often  seen,  and  lym- 
phatics have  been  shown  by  injection.  They  evidently  grow  into 
the  tissue  with  the  blood  vessels  and  there  is  no  reason  to  believe 
they  are  less  abundant  in  tumors  than  in  normal  tissues.  Nerve 
fibres  have  been  described  in  the  stroma  and  in  certain  cases  they 
represent  an  integral  part  of  the  tumor. 

ORIGIN.  A  tumor  arises  by  the  cells  of  a  certain  part  prolif- 
erating and  taking  on  the  characteristics  of  a  tumor.  No  one  has 
ever  seen  the  beginning  of  a  tumor  nor  would  it  be  possible  to 
recognize  a  small  area  of  proliferating  cells  as  a  tumor.  It  is  im- 
possible to  say  whether  the  beginning  is  from  a  single  cell  or  a 


134 


PATHOLOGY 


group  of  cells  or  an  area  of  tissue.  When  the  tumor  arises  it  con- 
tinues to  grow  by  the  proliferation  of  its  own  tissue.  The  adjoin- 
ing tissue  of  the  same  character  may,  to  some  extent,  merge  with 
the  tumor  and  form  a  part  of  it.  It  is  only  in  epithelial  tumors 
that  this  apparent  change  in  the  adjacent  epithelium  is  seen;  in 
most  tumors  it  is  certain  that  there  is  no  transformation  of  adjacent 
tissue  into  the  tumor.  A  tumor  may  have  several  centres  of  origin 
which  in  the  further  course  of  development  become  merged  into 
a  single  growth. 

The  growth  of  the  tumor  may  be:  (i)  simply  expansive,  pushing 
aside  the  tissue  with  which  it  comes  in  contact,  the  connective 
tissue  forming  a  capsule  around  it  as  around  a  foreign  body,  or 
(2)  the  tumor  may  grow  by  infiltration,  rows  and  masses  of  cells 
extending  from  the  tumor  into  the  spaces  of  the  tissue  about  it. 
The  tumor  cells  growing  out  in  this  way  become  separated  from 
the  mass  and  form  independent  centres  of  growth  which  by  en- 
largement again  join  with  the  main  tumor.  A  tumor  growing  by 
expansion  shows  a  definite  line  of  demarkation  separating  it  from 
the  surrounding  tissue,  but  in  the  infiltrative  growth,  the  line 
between  the  tumor  and  the  normal  tissue  is  not  sharply  defined 
and  is  often  absent. 

TISSUE  CHANGES.  The  tissue  in  contact  with  the  tumor  shows 
various  changes.  In  part  it  is  merely  pushed  aside,  the  connective 
tissue  becoming  condensed  from  pressure;  again  the  cells  may  be- 
come deformed  and  atrophied,  and  there  may  be  necrosis  from 
compression  of  blood  vessels  or  because  of  the  greater  avidity  of 
the  tumor  cells  for  nutrition.  In  certain  cases  the  tissue  may 
disappear  before  it,  the  tumor  cells  seeming  to  produce  by  contact 
'a  definite  zymotic  histolysis.  Around  the  metastatic  tumors  in 
the  liver  these  two  modes  of  action  are  strikingly  shown.  There 
may  be  changes  similar  to  the  changes  around  foreign  bodies,  the 
formation  of  a  granulation  tissue  with  foreign  body  giant  cells 
which  show  a  marked  phagocytosis  for  the  cells  of  the  tumors. 
Lymphoid  cells  in  enormous  numbers,  and  even  diffuse  lymphoid 
tissue  with  germinal  centres,  may  be  found  at  the  edge  of  the  tumor 
and  extending  into  it.  Polynuclear  leucocytes  are  not  present  in 
any  considerable  numbers  around  or  within  the  tumor  save  in  those 
cases  in  which  there  is  ulceration  of  the  surface  with  infection. 
Necrotic  tissue  within  the  tumor  may  or  may  not  exert  a  positive 


TUMORS  135 

chemotaxis  for  the  leucocytes.  Where  surface  ulceration  takes 
place,  a  granulation  tissue  may  be  produced  by  the  stroma  and  the 
tumor  growth  extends  into  this;  but  in  other  cases  the  base  of  the 
ulcer  is  formed  by  the  tumor  tissue  with  a  line  of  necrosis  on  its 
surface. 

NUMBER.  Usually,  tumors  are  single,  but  there  may  be  multiple 
tumors  of  the  same  character  arising  from  a  single  tissue.  There 
is  a  marked  tendency  for  the  development  of  such  tumors  from  the 
connective  tissue  sheaths  of  the  nerves,  appearing  either  on  the 
nerve  trunks  or  on  the  small  nerves  of  the  subcutaneous  tissue. 
They  often  appear  to  develop  simultaneously  and  to  grow  at  the 
same  rate.  In  such  cases  the  conditions  which  give  rise  to  tumor 
growth  are  operative  not  at  one,  but  at  many  places.  More  rarely, 
several  tumors  of  a  different  character  are  found.  Such  cases  are 
sufficiently  frequent  to  show  that  the  presence  of  a  single  tumor 
does  not  prevent  the  formation  of  others. 

METASTATIC  OR  SECONDARY  TUMORS  of  the  same  character  as 
the  primary  tumor  may  develop  in  other  parts  of  the  body.  They 
represent  an  extension  of  the  primary  tumor  not  by  continuity  but 
by  the  conveyance  of  cells  or  tumor  tissue  to  other  places  by  means 
of  the  blood  or  lymphatics.  The  tissue  around  the  tumor  may  be 
sown  with  such  metastases  or  they  may  occur  in  more  remote  parts. 
These  metastases  are  not  determined  by  the  accident  of  cell  lodg- 
ment merely.  The  cells  must  find  conditions  favorable  for  growth; 
for  example,  the  metastases  may  be  confined  to  certain  organs  as  the 
bone  marrow  or  lymph  nodes,  even  when  we  must  assume  that  they 
have  been  carried  to  other  places  also.  The  development  of  metas- 
tases may  take  place  at  a  comparatively  late  period  of  tumor 
growth,  in  cases  where  the  physical  conditions  for  their  formation 
were  present  from  the  beginning.  The  metastatic  tumors  may 
show  a  much  greater  rapidity  of  growth  than  the  primary  and  may 
occur  in  great  numbers  in  every  part  of  the  body.  They  often  show 
considerable  differences  in  character  as  compared  with  the  primary 
growth.  The  tumor  cells  find  their  way  into  the  blood  chiefly  by 
means  of  penetration  of  the  tumor  into  the  lumina  of  vessels. 
Metastases  within  the  blood  vessels  forming  tumor  thrombi  are 
not  uncommon  and  give  origin  to  new  (embolic)  metastases.  In  a 
case  of  melanotic  sarcoma  observed  by  the  author,  with  innumerable 
metastases,  the  tumor  cells  in  the  blood  were  so  numerous  as  to  be 


136  PATHOLOGY 

evident  on  microscopic  examination  of  a  blood  spread.  Metastases 
within  the  blood  may  occur,  the  tumor  cells  growing  in  the  blood 
as  in  any  other  tissue.  Leukaemia  should  be  regarded  as  a  tumor 
of  the  blood  forming  organs  with  metastasis  in  the  blood  itself. 
Metastases  by  blood  convection  are  more  common  in  the  lungs 
and  in  the  liver  than  in  any  other  organs.  Metastases  by  lym- 
phatic stream  are  caused  by  the  entrance  of  tumor  cells  into  the 
lymph  spaces  and  lymphatics  of  the  adjoining  tissue  thus  appear- 
ing in  those  lymph  nodes  which  receive  the  lymphatics  from  the 
region  of  the  tumor.  The  cells  are  carried  into  the  sinuses  of  the 
node  and  in  these  the  metastatic  growth  usually  begins.  The 
nodes  may  prove  a  temporary  dam  to  the  extension,  but  with  the 
continued  tumor  growth  into  the  nodes  there  may  be  further  exten- 
sion by  means  of  the  efferent  lymphatics.  The  tumor  may  grow 
for  long  distances  within  the  lymphatic  vessels.  The  thoracic  duct 
may  be  filled  with  the  tumor,  or  there  may  be  a  network  of  tumor 
growth  filling  the  lymphatics  of  a  region  as  those  of  the  visceral 
pleura.  The  metastases  by  both  blood  and  lymph  vessels  may 
occur  in  places  opposed  to  the  direction  of  the  flow.  This  may 
be  due  to  gravity,  or  to  temporary  slowness  or  cessation  or  even 
reversal  of  the  current.  The  same  conditions  are  seen  with  other 
forms  of  emboli.  There  are  no  hard  and  fast  rules  governing  either 
the  occurrence  or  situation  of  metastases.  They  are  more  apt  to 
occur  the  more  cellular  and  rapidly  growing  is  the  primary  tumor, 
and  the  looser  the  relation  between  the  cells  and  the  intercellular 
substance.  Metastases  may  also  be  due  to  the  implantation  of 
cells  or  portions  of  tumor  over  a  surface  which  the  primary  tumor 
attacks  as  in  the  peritoneum  or  pleura.  In  the  case  of  such  metas- 
tases in  the  peritoneum,  their  situation,  influenced  by  gravity,  is 
more  frequent  in  the  pelvis  than  in  other  locations. 

A  tumor  is  a  local  disease.  The  growing  tissue  of  the  tumor, 
wherever  found,  is  the  disease,  and  it  is  evident  that  if  all  this 
material  were  removed  the  disease  would  be  cured.  This  end  is 
sought  by  surgical  interference,  but  notwithstanding  seemingly 
thorough  removal  of  the  growth,  it  often  recurs  at  the  site  of  opera- 
tion, and  even  after  an  interval  of  months  or  years.  There  are 
many  reasons  for  this.  It  is  impossible  to  say  just  how  far  the 
growth  extends  into  the  neighboring  tissues;  the  situation  of  the 
tumor  may  be  such  that  an  extended  removal  of  the  tissue  about 


TUMORS  137 

it,  which  possibly  contains  the  tumor  cells,  is  impossible;  cells  from 
the  tumor  may  be  separated  in  the  course  of  the  operation  and 
become  included  in  the  cicatrix;  or  the  apparently  recurring  tumor 
may  be  a  tumor  of  new  origin  not  connected  at  all  with  the  first. 
It  is  evident  that  the  younger  the  tumor  the  less  involvement  there 
is  of  the  surrounding  tissue,  and  the  more  successful  is  the  operation. 
It  is  also  evident  that  a  tumor  growing  by  expansion  can  be  more 
successfully  removed  than  if  the  growth  be  infiltrating. 

A  tumor  usually  has  the  characteristics  of  the  tissue  from  which 
it  arises  and  the  histological  examination  of  the  tumor  may  deter- 
mine the  tissue  of  origin.  A  tumor  arising  in  a  tissue,  for  example, 
the  connective  tissue,  may  approach  in  character  closer  to  the 
embryonic  than  the  adult  type  of  this  tissue. 

In  other  cases,  the  tumor  differs  totally  from  the  tissue  of  its  ap- 
parent origin.  In  the  situations  where  this  occurs,  misplaced  tissues 
which  in  some  cases  have  developed  into  the  type  of  the  normal 
adult  tissue,  and  in  others  remain  undeveloped,  are  not  infrequently 
found,  and  tumors  in  certain  instances  undoubtedly  arise  from 
such  embryonic  remains.  Adrenal  tissue  is  not  infrequently 
found  either  on  the  surface  of  the  kidney  or  enclosed  within  it. 
Tumors  showing  the  characteristics  of  adrenal  tissue  are  found  in 
the  same  relation  with  the  kidney.  Epithelial  tumors  may  be 
found  in  the  neck  far  removed  from  any  epithelial  structure  and 
undoubtedly  arise  from  remains  of  the  epithelium  of  the  branchial 
arches. 

DEGENERATION.  The  cells  of  tumors  may  show  the  same  types 
of  degeneration  which  are  seen  in  other  pathological  conditions. 
Fat  is  very  commonly  found  in  the  cells,  but,  in  the  absence  of 
other  changes,  it  is  not  to  be  regarded  as  evidence  of  degeneration. 
The  same  is  to  be  said  with  regard  to  glycogen  and  to  the  various 
hyalin  masses  seen  within  the  cells.  In  cases  of  general  amyloid 
infiltration,  this  may  be  seen  in  the  tumor  also.  The  cells  in  the 
interior  of  epithelial  tumors  with  abundant  stroma  may  show 
atrophy  in  various  degrees  due  to  deprivation  of  blood  supply 
and  may  even  disappear.  The  most  common  pathological  condition, 
however,  is  necrosis.  This  may  affect  single  cells  or  groups  of 
cells  or  masses  of  tissue.  The  necrotic  areas  may  be  infiltrated 
by  leucocytes,  or  these  may  be  absent  and  no  reaction  whatever 
be  seen  in  the  surrounding  tissue.  The  necrotic  cells  may  form  a 


138  PATHOLOGY 

mass  of  granular  detritis  in  which  lime  salts  may  be  deposited,  or 
they  may  undergo  histolysis  and  be  removed  by  absorption.  We 
do  not  see  the  definite  tissue  reactions  which  are  associated  with 
repair  and  regeneration.  Necrosis  may  be  especially  marked  in 
rapidly  growing  tumors;  death  and  absorption  in  the  centre  may 
almost  keep  pace  with  the  rapid  growth  of  the  periphery.  The 
most  common  cause  of  necrosis  in  tumors  is  disturbance  of  the 
circulation  by  compression  of  the  thin-walled  vessels,  but  extensive 
necroses  which  we  are  not  able  to  attribute  to  this  are  sometimes 
seen. 

CELL  CHARACTER  AND  FUNCTION.  The  cells  of  a  tumor  repeat  to 
a  greater  or  less  degree  the  morphology  and  arrangement  of  the 
cells  of  the  tissue  from  which  the  tumor  arises.  Thus,  in  a  tumor 
arising  from  a  surface  covered  with  cylindrical  epithelium,  the  cells 
are  generally  cylindrical  in  shape  and  arranged  in  contact  with  each 
other  along  the  long  axis.  The  cells  of  a  tumor  of  the  adrenal  gland 
show  the  characteristics  of  the  cells  of  the  gland.  They  may  show 
some  of  the  functions  of  the  tissue,  but  this  relationship  is  less  evi- 
dent than  is  the  morphological.  In  tumors  arising  from  the  connec- 
tive tissue,  the  intercellular  substances  are  produced;  in  those  arising 
from  nonstriated  muscle,  myoglia  fibrils  are  formed;  and  in  those 
arising  from  neuroglia,  the  characteristic  glia  fibrils  are  formed; 
the  bone  tumors  produce  bone,  and  the  cartilaginous  tumors, 
cartilage.  In  tumors  which  arise  from  the  surface  epithelium,  the 
cells  show  the  same  differentiation  ending  in  the  formation  of 
keratin  as  the  normal  cells  of  the  surface.  In  tumors  of  the  adrenal 
glands,  epinephrin  is  formed;  in  tumors  of  the  thyroid,  iodothyrein; 
in  some  of  the  adenomata  of  the  liver,  bile  may  be  found  in  the 
cells;  in  tumors  arising  from  the  hypophysis  and  the  pineal  gland, 
changes  are  found  in  the  body  indicating  the  action  of  substances 
produced  in  these  organs.  The  cells  may  produce  large  quantities 
of  mucin,  and  this  may  appear  also  in  the  intercellular  substance. 
Function  is,  however,  always  subordinate  to  growth;  the  energy 
of  growth  controls.  Of  the  production  of  substances  other  than 
those  of  definite  chemical  composition  or  whose  presence  can  be 
recognized  by  specific  action,  we  have  little  knowledge.  The 
chemical  investigation  of  tumors  has  thrown  little  or  no  light  on  the 
subject,  and  what  study  has  been  made  on  the  metabolism  of 
individuals  with  tumors  has  also  been  without  definite  results. 


TUMORS  139 

Histolytic  and  haemolytic  ferments  have  been  found  in  tumors,  and 
in  the  early  stages  of  carcinoma  haemolytic  agents  have  been  de- 
scribed in  the  blood.  Evidence  for  the  production  of  specific 
injurious  substances  in  tumors  is  found  in  the  condition  of  cachexia, 
a  state  of  general  malnutrition  and  anaemia,  which  is  often  seen  in 
the  late  stages  of  the  malignant  tumors.  There  are  many  condi- 
tions accompanying  such  tumors  which  may  bring  about  cachexia 
without  the  necessity  for  the  supposition  of  specific  activity  of  the 
tumor  cells,  as,  for  example,  superficial  ulceration  and  bacterial  in- 
vasion, the  closure  of  important  canals,  the  destruction  of  organs, 
the  absorption  of  necrotic  products,  pain  and  sleeplessness.  This 
cachexia  need  not  appear,  and  may  be  absent  when  all  the  con- 
ditions favoring  it  seem  to  be  present.  The  tumor  cells  like  other 
living  cells  receive  from  their  environment  the  forces  on  which 
their  activity  depends  and  give  off  the  products  of  metabolism. 
What  these  are,  whether  there  is  any  common  product  associated 
with  the  excessive  growth  activity  or  whether  every  tumor  differs 
in  this  regard,  we  do  not  know.  The  absence  of  evidence  of  the 
presence  of  such  abnormal  substances  is  no  proof  that  they  are 
not  present.  The  organism  may  have  adapted  itself  to  the  presence 
of  such  substances  or  they  may  be  destroyed  as  they  are  formed. 
The  autopsy  findings  in  deaths  from  tumors  have  not  thrown  any 
light  on  this  question.  Terminal  infection  is  common,  the  changes 
in  the  organs  are  in  no  sense  characteristic  and  admit  of  ready 
explanation  by  the  accessory  conditions  present  at  the  time  of 
death. 

RELATION  TO  ENVIRONMENT.  The  tumor  cell  is  not  indifferent  to 
the  environment  which  the  host  offers.  The  variations  in  the  activity 
of  growth  and  formation  of  metastases,  the  unaccountable  necrosis 
which  may  take  place  and,  in  certain  cases,  the  disappearance  of 
the  tumor,  all  show  this  to  be  true.  The  relation  of  certain  tumors 
to  the  age  of  the.  individual  is  another  instance.  The  very  common 
myomata  of  the  uterus  most  usually  appear  during  the  period  of 
sexual  activity,  and  growth  of  such  tumors  may  either  cease  or  very 
greatly  diminish  when  the  period  of  sexual  activity  is  past.  Tumors 
of  the  mammary  gland  often  show  an  excessive  growth  during 
pregnancy  thus  showing  that  the  tumor  cells  also  are  influenced 
by  the  agents  which  induce  the  glandular  activity  of  the  organ. 
There  must  be  an  adaptation  of  the  tumor  to  the  individual  which 


140  PATHOLOGY 

leads  to  the  symbiosis  of  tumor  with  host.  In  the  tumors  of  animals 
it  has  been  shown  that  the  adaptation  extends  to  the  species,  but 
never  beyond  this.  In  man  the  adaptation  is  individual,  all  at- 
tempts which  have  been  made  to  transplant  human  tumors  in 
animals  and  in  other  individuals  having  been  unsuccessful.  The 
metastases  show,  however,  that  there  is  more  than  a  local  adapta- 
tion, and  successful  implantation  has  been  made  of  the  tumor 
tissue  into  a  remote  part  of  the  individual  who  bears  the  tumor. 

INFECTION.  Little  is  known  as  to  the  resistance  of  tumor  tissue 
to  infection.  Pathogenic  organisms  are  often  found  in  tumors  ex- 
tending from  surface  ulceration  or  carried  into  them  by  the  circu- 
lation. Enormous  necroses  may  be  associated  with  the  presence 
of  pyogenic  bacteria.  In  one  case  observed  by  the  author,  nearly  the 
whole  mass  of  a  large  sarcoma  of  the  thigh  became  necrotic  after  the 
injection  of  a  virulent  streptococcus  into  the  tumor  for  therapeutic 
purposes.  There  have  not  been  sufficient  observations  to  determine 
whether  the  tissue  of  a  tumor  represents  essentially  new  tissue  or 
whether  it  shares  in  the  characteristics  which  the  other  tissues  have 
acquired,  as  in  the  case  of  general  immunity.  Numbers  of  observa- 
tions on  the  experimental  tumors  of  animals  seem  to  show  an  extraor- 
dinary resistance  of  the  cells.  But  it  is  not  possible  to  determine  the 
viability  of  the  cells  of  human  tumors  by  transplantation.  So  far 
as  tissue  study  can  tell  us,  the  cells  of  human  tumors  show  no 
special  resistance  to  conditions  producing  death  and  disintegration 
in  other  tissues.  The  tissue  of  one  tumor  is  not  immune  from 
metastases  coming  from  a  different  tumor.  I  have  several  times 
found  carcinoma  metastases  in  a  myoma  of  the  uterus.  Nor  does 
an  infectious  disease  confer  immunity  against  tumor  formation. 
The  supposed  antagonism  between  tuberculosis  and  carcinoma  is 
due  merely  to  the  difference  in  the  age  period  when  these  two 
diseases  are  most  common. 

INHERITANCE.  Little  is  known  with  regard  to  inheritance  in 
tumors.  Studies  on  the  tumors  of  mice  show  a  greater  suscepti- 
bility to  tumor  formation  in  the  offspring  of  mice  with  spontaneous 
tumors.  Some  studies  carried  out  on  human  families  seem  to  show 
some  positive  influence  on  the  descendants,  but  in  the  frequency 
of  tumors  such  statistical  evidence  is  of  little  value.  The  question 
has  much  bearing  on  the  origin  of  tumors.  If  the  tumor  be  merely 
an  acquired  condition  due  entirely  to  the  action  of  causes  extraneous 


TUMORS  141 

to  the  organism,  there  would  be  no  hereditary  influence;  if,  on 
the  other  hand,  there  is  a  special  congenital  predisposition  of  the 
tissues,  whether  in  the  cells  themselves  or  in  the  fluids,  arising  as  a 
variation,  and  associated  with  or  underlying  the  tumor  formation, 
we  should  expect  an  hereditary  influence.  The  question  is  one 
which  should  be  and  can  be  determined. 

FREQUENCY.  The  question  as  to  whether  tumors  are  increasing 
is  equally  difficult  of  solution.  Vital  statistics  in  every  country 
seem  to  show  an  increase.  The  statistics  of  Massachusetts  show 
between  1855  and  1905  an  increase  of  400  per  cent.  There  are 
many  factors,  such  as  the  increasing  duration  of  life,  the  increasing 
certainty  of  diagnosis,  the  variation  in  the  reliability  of  vital 
statistics,  the  movement  of  the  population,  etc.,  which  are  all  difficult 
to  estimate,  and  which  must  be  considered  in  such  statistics.  The 
same  may  be  said  of  the  evidence  for  the  greater  frequency  of 
tumors  in  general  or  of  certain  tumors,  in  different  countries  and 
localities.  The  opinion  generally  prevails  that  tumors  are  more 
numerous  in  highly  civilized  than  in  uncivilized  peoples,  but  among 
the  uncivilized  no  reliable  method  exists  for  determining  frequency. 

No  age  is  immune  from  tumors.  They  may  be  present  at  birth 
or  their  development  may  begin  shortly  afterwards.  From  five  to 
twenty  is  the  most  immune  age,  that  from  forty-five  to  sixty-five 
the  most  susceptible  to  the  malignant  tumors.  Certain  types  of 
tumors  predominate  at  different  ages.  The  connective  tissue  tumors 
tend  to  appear  at  an  earlier  age  than  those  arising  from  the 
epithelium. 

ETIOLOGY.  We  know  nothing  as  to  the  aetiology  of  tumors.  Any 
cause  must  apply  to  all  tumors,  for  the  character  of  growth  is  com- 
mon to  all,  just  as  there  are  common  conditions  in  infections.  No 
sufficient  evidence  has  been  brought  forward  to  show  that  they 
are  due  to  parasitic  organisms.  Various  forms  of  bacteria  and 
other  organisms  have  been  found  in  tumors,  but  with  no  constancy; 
and  no  tumors  have  been  produced  by  inoculating  with  parasites. 
All  the  various  sorts  of  cell  inclusions  which  have  been  considered 
as  protozoal  parasites  of  unknown  character  have  been  shown  not 
to  be  such.  Support  for  the  parasitic  theory  is  found  in  the  fact 
that  parasites  can  excite  proliferation  of  tissue  and  produce  growths, 
but  such  growths,  though  they  show  some  similarity  to  tumors,  lack 
the  distinguishing  characteristics.  No  parasite  has  even  been 


142  PATHOLOGY 

found  which  can  so  alter  the  cells  that  the  stimulus  to  growth  given 
by  the  presence  of  the  parasite  will  in  the  absence  of  the  parasite 
be  transmitted  to  the  descendants  of  the  cells.  The  parasitic 
theory  would  be  difficult  of  application  in  the  case  of  the  con- 
genital tumors.  The  theory,  however,  though  at  present  lacking 
ground  for  belief,  should  not  be  dismissed  as  an  impossible  one. 

Trauma  as  a  direct  cause  of  tumors,  so  changing  the  cells  that 
they  at  once  take  on  the  characteristics  of  tumor  cells,  can  be 
dismissed.  There  is  too  little  ground  for  its  support. 

There  are,  however,  a  number  of  conditions  which,  though  not 
immediately  operative,  may  so  alter  the  tissues  as  to  make  them 
susceptible  to  the  action  of  another  factor.  Trauma,  or  injury  of 
tissue,  may  be  considered  in  this  regard.  There  is  an  undoubted 
relation  between  tissue  injury  and  tumors.  Injurious  agents  which 
are  continuous  and  slow  in  their  action,  and  which  produce  continu- 
ous injury  with  equally  continuous  regenerative  growth,  are  most 
effective  in  this  respect.  Tissues  become  separated  in  this  way 
from  their  normal  relations  with  one  another.  Metaplasia  of 
tissue  often  takes  place  and  there  is  a  tendency  for  tumor  develop- 
ment in  such  metaplasia.  The  tumor  at  the  site  of  the  injury  may 
appear  after  years  have  elapsed.  In  certain  cases  the  injurious 
agents  seem  to  have  a  specific  relation  to  tumor  formation,  as  in- 
juries by  Roentgen  rays,  by  the  chemical  injuries  of  coal  products 
as  shown  by  chimney  sweepers'  carcinoma  of  the  scrotum,  by  the 
epithelial  tumors  of  the  skin  and  bladder  in  aniline  workers.  Para- 
sites, such  as  the  Bilharzia  Haematobium,  may  produce  changes  in 
tissue  which  afterwards  become  the  seat  of  tumors. 

The  germinal  theory  prominently  associated  with  the  name  of 
Cohnheim  must  be  considered  in  this  respect.  This  is  not  a  causal 
theory,  the  cause  being  the  agency  which  produces  the  peculiar 
character  of  growth  constituting  the  tumor.  The  theory  of  Cohn- 
heim refers  the  origin  of  all  tumors  to  remains  of  embryonic  tissue, 
or  to  tissue  which  in  the  course  of  development  has  become  mis- 
placed. There  is  much  in  favor  of  this.  There  is  a  frequent  —  too 
frequent  to  be  chance  —  combination  between  malformations  of 
various  sorts  and  tumors.  The  peculiar  congenital  rhabdomyoma 
of  the  heart  is  probably  constantly  associated  with  malformations 
of  the  central  nervous  system.  Tumors  frequently  arise  in  places 
where  there  are  complicated  processes  of  development,  as  in  the 


TUMORS  143 

regions  of  the  embryonic  fissures,  and  where  two  sorts  of  embryonic 
tissue  join.    They  often  develop  from  accessory  organs  as  those 
related  to  the  mamma,  the  adrenal  gland,  the  pancreas,  the  thy- 
roid and  parathyroid.     An  excessive  or  misplaced  tissue  germ 
usually  becomes  either  lost  by  gradual  atrophy  or  it  becomes  dif- 
ferentiated simultaneously  with  the  normal  tissue  into  an  accessory 
organ,  or  the  differentiation  may  be  so  late  that  it  forms  a  cyst  as 
the  dermoid  cysts.    There  is  really  no  close  analogy  between  tumor 
cells  and  embryonic  cells.    Both  show  rapidity  of  growth,  but  the 
embryo  cell  growth  proceeds  to  differentiation.    Ribbert  carried 
the  theory  of  Cohnheim  much  further,  assuming  an  origin  for  tumors, 
not  only  in  such  misplaced  embryonic  tissue,  but  in  cells  and  tissue 
which,  in  consequence  of  trauma,  or  continued  or  long-standing 
inflammation,  had  become  separated  from  their  organic  relations. 
All  sorts  of  experiments  have  been  made  by  design  and  accident  in 
which  cells  and  tissues  have  been  separated  from  their  normal 
relations;  but  a  tumor  has  never  been  produced,  nor  has  a  tumor 
by  any  other  procedure  been  produced  experimentally.     It  is  not 
impossible  that  two  conditions  are  essential  to  tumor  formation, 
a  tissue  capable  of  growth,  and  an  agency  acting  on  this  which 
causes  growth. 

CLASSIFICATION.  Some  clinical  purpose  may  be  served  by  a 
division  of  tumors  into  those  which  are  benign  and  those  which 
are  malignant.  Such  a  division  of  tumors  has  very  decided  limi- 
tations. Strictly  speaking,  there  are  no  benign  tumors.  The 
situation  is  of  great  importance^  A  slow-growing  tumor  without 
infiltration  and  without  producing  metastases  may  cause  serious 
damage  by  the  pressure  which  it  exerts  on  important  organs;  for 
example,  a  slow-growing  fibrous  tumor  of  the  dura.  Apart  from 
malignancy  due  to  situation,  the  criteria  are  rapid  growth,  infil- 
tration of  surrounding  tissue  and  formation  of  metastases.  The 
results  of  microscopic  examination  are  not  always  conclusive  in  de- 
termining malignancy. 

Classification  of  objects  always  serves  a  useful  purpose.  It 
facilitates  study  and  comprehension  if  the  objects  can  be  arranged 
into  groups,  each  group  including  a  number  of  factors  common  to 
all  its  members.  So  great  is  the  diversity  of  structure  in  tumors, 
so  uncertain  in  many  cases  is  the  histogenesis,  that  a  classification 
based,  as  is  the  classification  of  the  normal  tissues,  on  structure 


144  PATHOLOGY 

and  histogenesis  presents  great  difficulties.  Nearly  every  one  who 
has  written  on  tumors  gives  a  classification  differing  in  various 
ways;  but  in  any  classification,  individual  tumors  which  cannot 
be  placed  will  be  found.  A  definition  of  tumors  cannot  be  made 
on  structure  alone,  but  the  character  of  growth  must  enter  into  it. 
If  the  aetiological  factors  were  known,  there  would  be  some  com- 
mon and  certain  point  from  which  to  start.  The  anatomical 
classification  of  the  lesions  of  tuberculosis  was  utterly  confused 
until  the  discovery  of  the  bacillus  gave  the  possibility  of  a  classi- 
fication based  on  a  common  aetiology.  Various  names  of  tumors, 
which  usage  has  so  fixed  that  they  cannot  be  rejected,  have  come 
down  to  us  from  the  past.  The  name  "carcinoma"  or  "cancer," 
which  was  given  to  certain  tumors  because  of  the  fancied  resem- 
blance of  the  dilated  overlying  subcutaneous  veins  to  the  out- 
stretched legs  of  a  crab,  is  used  loosely  to  signify  a  malignant 
tumor  of  any  character  and  specifically  as  a  name  for  a  malignant 
tumor  derived  from  epithelium.  The  name  "sarcoma,"  now 
generally  used  to  signify  a  tumor  originating  in  the  connective 
tissue,  but  differing  in  various  ways  from  the  normal  type  of  this 
tissue,  was  originally  used  to  designate  a  tumor  of  a  fleshy  char- 
acter. Virchow,  with  his  great  experience  and  wide  comprehension, 
divided  all  tumors  into  three  groups.  The  histoid  group,  em- 
bracing those  tumors  composed  in  whole  or  in  great  part  of  a  single 
tissue  similar  in  character  to  some  one  of  the  normal  tissues;  the 
organoid  group,  into  whose  structure  two  or  more  tissues,  arranged 
in  a  certain  order,  entered;  the  teratoid  group,  into  whose  structure 
systems  of  tissue  entered  and  which  formed  the  connecting  link 
between  tumors  and  monstrosities.  The  classification  must  be 
based  so  far  as  possible  on  similarity  of  structure  to  the  normal 
tissues,  and  the  histogenesis,  as  far  as  this  can  be  ascertained,  should 
also  enter  into  it.  Histogenesis,  even  of  normal  tissue,  is  not  on 
an  absolutely  certain  basis  and  still  less  certain  is  it  in  the  case  of 
tumors.  The  analogy  of  tumor  structure  with  that  of  normal 
tissue  is  found  in  the  character  and  arrangement  of  the  cells  and 
the  formation  and  character  of  the  intercellular  substances. 


TUMORS 


145 


The  following  classification  of  tumors  based  on  character  and  em- 
bryonic origin  of  the  tissue  is  the  simplest  and  generally  adopted. 

Fibroma 

Myxoma 

Chondroma 

Osteoma 

Lipoma 

(  Leiomyoma 
1  Rhabdomyoma 

Melanoma 

Angioma 

Sarcoma — this  name,  used  partly  alone,  partly  as 
an  appendage  to  other  names,  as  fibro-sarcoma, 
myxo-sarcoma,  etc.,  designates  tumors  of  the 
connective  tissue  group  which  vary  widely  from 
the  normal  type  of  these  tissues,  in  relation  of 
cells  and  intercellullar  substance,  and  in  rapidity 
of  growth. 


Tumors  of  the 

Connective  Tissue^ 

Class. 


Myoma 


Tumors  of  Epithelium 


Papilloma 

Adenoma 

Carcinoma 

Chorioepithelioma 

Hypernephroma 


Tumors  of  the  J  Neuroma 
Nervous  Tissues  j  Glioma 


Tumors  of  the 
Blood  Tissues 


Lymphoma 
Chloroma 
Myeloma 
Leucocytoma 


Tumors  of  Endothelium  { Endothelioma 

Tumors  of  Embryonic  ( ,„    , 

\  Lmbry 
Character  of  Tissue    | 


oma 


TERATOMATA  are  tumors  of  embryonic  tissues,  but  which  have 
to  a  greater  or  less  degree  developed  in  a  normal  manner  and  which 
show  a  coordination  of  structure. 

It  cannot  be  pretended  that  such  a  classification  as  this  is  scien- 
tific, it  is  merely  pragmatic. 


146  PATHOLOGY 

Tumors  have  been  found  in  most  of  the  mammalia  both  those  in 
domestication  and  in  the  feral  state.  They  have  also  been  found 
in  some  of  the  cold-blooded  vertebrates.  The  tumors  found  vary 
in  structure  and  in  character  of  growth.  They  have  so  much  in 
common  with  tumors  of  man  that  they  fall  into  the  nomenclature 
of  human  tumors.  There  seems  to  be  some  relation  between  the 
tumor  character  and  genus;  thus,  in  fowls  tumors  of  the  lymphoid 
type  are  most  common.  Metastases  occur  and  chiefly  by  the  blood, 
but  not  with  the  frequency  which  is  seen  in  human  tumors.  The 
presence  of  one  tumor  confers  no  immunity  from  the  occurrence 
of  other  spontaneous  tumors.  They  show  a  decided  difference 
from  the  tumors  in  man  in  that  the  adaptation  between  tumor  and 
host  tissue  extends  to  the  species.  But  it  does  not  go  beyond  this. 
Even  within  the  species  the  adaptation  may  be  limited  to  certain 
strains.  These  tumors  may  be  transplanted  from,  one  individual 
of  a  species  to  another  by  placing  beneath  the  skin  or  in  other 
suitable  situations  cells  or  portions  of  the  tumor  tissue  which  grow 
in  the  new  situation.  The  process  is  comparable  not  to  the  inocu- 
lation of  parasites,  but  to  the  grafting  of  plant  tissue.  Tumors  of 
a  simple  structure  corresponding  with  Virchow's  histoid  group  are 
less  easily  transplanted;  their  adaptation  may  be  confined  to  the 
bearer.  The  virulence  of  the  tumors,  i.e.,  their  capacity  for  growth 
and  for  overcoming  the  resistance  of  the  tissues,  may  be  increased 
by  constant  transplantation.  The  resistance  of  the  animal  to  the 
implantation  may  by  various  procedures  be  increased  up  to  the 
production  of  complete  immunity.  After  spontaneous  recovery 
from  a  tumor  immunity  is  established  and  may  be  passively  trans- 
ferred by  means  of  the  serum  of  the  resistant  animal  to  another. 
Immunity  may  be  given  by  a  previous  inoculation  with  another 
nonvirulent  tumor,  it  may  also  be  given  by  a  previous  inoculation 
of  the  animal  with  fcetal  and  even  with  adult  tissue.  The  immunity 
is  not  specific.  Immunity  against  one  sort  of  tumor  will  protect 
against  a  tumor  of  different  character.  In  the  course  of  trans- 
plantation a  tumor  may  change  its  character,  a  carcinoma,  for 
instance,  changing  into  a  sarcoma.  Most  prominently  there  has 
been  shown  that  in  tumor  growth  there  must  be  an  adaptation 
between  tumor  tissue  and  host.  The  possibility  of  adaptation 
varies  and  may  be  experimentally  increased  or  diminished. 


CYSTS 

These  have  so  much  relationship  to  tumors  that  the  general 
subject  may  be  considered  here  while  the  special  forms  will  be  con- 
sidered in  the  special  pathology  of  the  organs.  A  cyst  is  a  collec- 
tion of  fluid  or  semifluid  material  in  a  circumscribed  cavity  in  the 
tissues.  It  is  evident  that  cysts  may  arise  in  various  ways  and  may 
be  divided  into: 

RETENTION  CYSTS  represent  a  collection  of  fluid  in  a  gland  or  a 
duct  or  any  epithelial-lined  structure  due  to  closure  of  ducts  and 
the  retention  of  the  products  of  secretion.  Such  products  may  be 
so  changed  as  to  offer  but  little  similarity  to  the  normal  secretion. 
There  is  a  growth  of  epithelium  which  keeps  pace  with  the  enlarging 
cavity  and  often  exceeds  it.  The  wall  is  thickened  by  a  reactive 
growth  of  connective  tissue,  the  surface  may  be  round  and  smooth 
or  irregular  with  projections  into  the  surrounding  tissue,  as,  for 
example,  in  cysts  of  the  pancreas. 

EXTRAVASATION  CYSTS  are  due  to  haemorrhage  in  the  tissue. 
After  the  absorption  of  the  blood  a  cavity  filled  with  tissue  fluid 
may  result  due  to  the  inability  of  the  walls  to  collapse  as  in  the  case 
of  the  brain.  Example,  apoplectic  cyst. 

EXUDATION  AND  TRANSUDATION  CYSTS  are  due  to  the  accumu- 
lation in  a  cavity  of  an  exudation  or  an  increased  transudation. 
Example,  hydrocele. 

CYSTS  FROM  SOFTENING  AND  DISINTEGRATION  OF  TISSUE  may 
arise  in  a  tumor,  or  in  any  organ  of  the  body,  as  in  the  brain.  After 
cerebral  softening  cysts  always  appear. 

CONGENITAL  CYSTS  may  be  present  at  birth  or  develop  after- 
wards. They  are  due  to  disturbances  in  development  in  conse- 
quence of  which  tissues  may  be  isolated  and  enclosed  in  a  different 
tissue,  and  in  consequence  of  cellular  activity  a  secretion  is  formed 
and  included  in  the  tissue.  Example,  dermoid  cyst  of  the  skin. 
Or  there  is  imperfect  formation  of  canals.  Example,  congenital 
cystic  kidney.  Or  there  may  be  persistence  of  embryonic  canals 
or  tissues  which  should  have  disappeared  in  development.  Ex- 
ample, cysts  of  neck  arising  from  remains  of  branchial  arches, 

147 


148  PATHOLOGY 

cysts  of  vagina  formed  by  remains  of  Mullers  ducts.    There  is  no 
sharp  line  separating  the  cysts  from  the  tumors. 

CYSTIC  TUMORS  are  tumors  in  which  the  presence  of  fluid  in 
closed  spaces  is  a  prominent  characteristic.  The  fluid  is  due  to 
the  activity  of  the  tumor  cells.  Example,  cystic  tumor  of  ovary. 


CONNECTIVE  TISSUE  TUMORS 

FIBROMA,  a  tumor  originating  in  the  connective  tissue  and  con- 
forming in  structure  to  the  type  of  this  tissue.    The  tumor  is 
composed  of  cells,  intercellular  substances  in  fibrillar  form  and 
vessels.     Such  tumors  may  form  in  any  part  of  the  body,  but  they 
are  most  common  in  the  subcutaneous  connective  tissue  and  in  the 
corium.     They  may  be  perfectly  circumscribed  or  closely  connected 
with  the  surrounding  tissue.    Three  forms  of  fibroma  are  recog- 
nized, the  fibroma  molle,  fibroma  durum  and  keloid.    The  fibroma 
molle  is  a  soft  elastic  tumor  composed  of  delicate  interlacing  fibrils, 
a  varying  amount  of  tissue  fluid,  sometimes  so  abundant  as  to  give 
rise  to  the  name  cedematous  fibroma,  the  cells  generally  of  spindle 
shape  lying  in  close  relation  to  the  fibrils.    The  blood  vessels  are 
abundant  and  there  is  frequently  a  condensation  of  the  tissue 
about  them.     The  fibroma  durum  is  a  hard  tumor,  on  section  white 
and   refractile,  with  interlacing   connective   tissue  bands.      The 
intercellular  substance  is  composed  of  bands  of  coarse  fibres  which 
apparently  are  formed  by  the  fusion  of  single  fibrills,  the  cells  are 
small,  the  nuclei  elongated,  the  cytoplasm  not  evident,  and  they 
lie  either  within  or  on  the  outside  of  the  bands  of  fibres.     Cross 
sections  of  the  bands  resemble  sections  of  tendon.    The  vessels 
are  not  numerous.     The  keloid  is  a  hard,  dense,  white  tumor  often 
arising  from  scars  and  in  structure  closely  resembling  scar  tissue. 
It  is  composed  of  closely  interwoven  bands  of  large,  dense  fibres 
with  few  and  small  cells  lying  chiefly  in  the  interstices.    The  vessels 
are  few.    These  tumors  are  more  common  in  negroes,  particularly 
in  those  living  in  the  tropics.    A  special  form  of  fibroma  arises 
from  the  connective  tissue  of  nerves.     These  tumors  usually  are 
multiple,  often  appear  simultaneously,  and  may  affect  either  the 
larger  nerves  or  the  small  nerves  in  the  subcutaneous  tissue  or 
both.    The  tumor  is  of  importance  chiefly  in  that  it  serves  as  the 
type  of  the  systemic  tumors.    Thousands  of  small  or  large,  often 
pendulous,  soft  tumors  may  appear  in  the  subcutaneous  tissue. 
Along  the  nerves  the  tumors,  often  in  great  numbers,  form  hard, 
round  or  spindle-shaped,   circumscribed  masses,  and  where  the 

149 


150  PATHOLOGY 

nerves  pursue  a  tortuous  course,  irregular,  convoluted,  interlaced 
masses  (plexiform  neuroma).  The  nerve  fibres,  which  take  no 
part  in  the  tumor  growth,  may  pass  over  the  surface  or  in  bundles 
through  the  interior. 

The  fibroma  has  no  relation  to  age  and  does  not  tend  to  recur  after 
removal  save  in  those  cases  where  the  limits  of  the  tumor  are  not 
sharp  or  where,  from  the  situation,  complete  removal  is  difficult. 
It  does  not  produce  metastases.  There  is  every  gradation  between 
the  fibromata  and  the  sarcomata  in  relative  numbers  of  cells,  and 
in  the  relations  of  the  cells  to  the  intercellular  substances.  To 
such  intermediate  tumors  the  name  fibrosarcoma  is  given. 

The  close  relation  between  the  normal  epithelium  and  connective 
tissue  may  be  repeated  in  tumors.  The  fibroma  of  the  skin  may 
develop  in  the  subcutaneous  tissue  or  in  the  lower  corium  or  in  the 
papillary  layer.  In  the  latter  case  the  papillae  grow  with  the 
tumor  and  may  become  elongated,  enlarged  and  give  off  numerous 
branches.  The  name  PAPILLOMA  is  given  to  the  tumors  in  which 
the  growth  of  the  papillae  is  the  most  marked  characteristic.  There 
is  an  accompanying  new  formation  of  epithelium  which  may 
greatly  exceed  the  normal.  It  is  possible  to  divide  the  fibro- 
epithelial  tumors  into  two  groups  depending  upon  the  tissue  which 
has  the  dominating  place  in  growth.  The  subject  is  also  considered 
under  adenoma.  Fibromata  developing  beneath  mucous  surfaces 
form  pendulous  projections  called  polypi.  The  fibrous  tissue 
usually  is  soft  and  cedematous  and  may  contain  much  mucin 
giving  to  the  growth  a  gelatinous  translucent  character.  The 
surface  epithelium  rarely  shows  an  excessive  growth,  but  when 
glands  are  present  there  may  be  much  new  formation  of  glandular 
tissue.  In  certain  cases  it  is  difficult  to  say  whether  the  connective 
tissue  or  the  epithelial  growth  is  the  dominant  factor.  Such  tumors 
are  best  classed  under  the  name  fibro-epithelial  tumors,  and  there 
is  no  morphological  distinction  between  them  and  similar  combined 
connective  tissue  and  epithelial  growth  due  to  chronic  irritation 
often  of  infectious  character. 

Very  similar  growths  are  found  in  glandular  organs,  particularly 
in  the  mamma.  A  growth  of  the  connective  tissue  here  will  extend 
into  the  ducts  and  acini  of  the  gland.  These  become  greatly 
dilated  and  filled  with  a  complicated  branching  mass  of  papillae 
appearing  on  section  as  isolated  masses  of  fibrous  tissue  covered 


CONNECTIVE  TISSUE  TUMORS  151 

with  epithelium.  The  epithelial  growth  may  be  in  excess  and 
spaces  corresponding  to  acini  appear  within  it.  These  tumors 
usually  are  circumscribed  and  on  section  show  numerous  fissures 
corresponding  to  the  dilated  ducts.  They  are  given  the  name 
" intracanalicular  fibroma"  or  when  the  epithelial  growth  is  exces- 
sive " intracanalicular  adeno-fibroma." 

MYXOMA;  a  tumor  of  the  connective  tissue  type  characterized 
by  the  presence  of  mucin  in  large  amount  in  the  intercellular  sub- 
stance. The  normal  type  of  this  tissue  is  found  in  the  umbilical 
cord.  These  tumors  may  form  in  the  connective  tissue  in  any 
part  of  the  body,  and  may  be  of  any  size.  They  vary  in  consis- 
tency and  have  a  transparent  gelatinous  appearance.  On  micro- 
scopic examination  there  is  always  a  varying  amount  of  fibrous 
intercellular  substance  and  a  clear  structureless  material  which 
stains  faintly  with  hematoxylin.  The  cells,  which  vary  much  in 
numbers  in  different  tumors  and  in  different  parts  of  the  same 
tumor,  are  spindle  or  stellate  in  form.  The  tumor  is  more  malignant 
than  the  ordinary  type  of  the  fibroma.  Blood  vessels  are  relatively 
abundant  and  extensive  haemorrhages  often  occur.  The  myxoma 
has  not  a  very  definite  place  in  the  list  of  tumors.  Mucin  is  found 
in  all  connective  tissue  and  in  varying  amounts  in  all  the  connective 
tissue  tumors.  It  may  be  increased  in  amount  in  tissues  under- 
going atrophy  as  in  atrophy  of  fat.  Myxomatous  tissue  occurs 
more  often  in  tumors  in  combination  with  other  types  of  tissue 
as  fat,  cartilage,  bone,  than  in  pure  form.  Its  presence  is  recognized 
in  the  nomenclature  in  combination  with  other  tumor  names  as 
myxofibroma,  etc. 

LIPOMA;  a  tumor  composed  of  fat  tissue.  Most  common  in 
subcutaneous  tissue,  but  may  be  found  in  the  internal  fat  and 
rarely  in  places  where  fat  is  not  normally  present,  as  in  the  brain, 
spinal  canal  or  in  the  interior  of  organs.  In  these  latter  places 
it  undoubtedly  arises  from  fat-forming  tissue  which  was  misplaced 
in  the  course  of  embryonic  development.  The  tumors  are  smooth 
on  the  exterior,  round  or  lobulated,  and  so  loosely  connected  with 
the  surrounding  tissue  that  they  may  change  their  position  by 
gravity  and  form  new  vascular  connections.  They  are  rather  more 
yellow  than  the  normal  fat.  Fibrillar  connective  tissue,  always 
present,  varies  in  amount  being  sometimes  so  abundant  that  the 
name  fibrolipoma  is  used.  The  cells  usually  are  larger  than  normal 


1 52  PATHOLOGY 

fat  cells  and  there  seem  to  be  centres  of  growth  where  the  cells 
are  small  and  the  fat  in  small  droplets  in  the  cytoplasm.  The 
pure  lipomata  may  appear  at  any  age,  they  have  few  vessels,  grow 
slowly  and  constitute  the  type  of  benign  tumors.  The  largest 
lipomata  are  those  which  appear  as  circumscribed  tumor  masses 
in  the  retro-peritoneal  fat.  A  special  form  of  lipoma,  known  as 
xanthom-a,  occurs  in  the  skin,  especially  on  the  eyelids,  in  the  form 
of  small,  circumscribed,  flat,  yellowish-brown  tumors.  Micro- 
scopically, the  cells  contain  yellow  pigment  and  fat  in  the  form  of 
small  droplets. 

Fat  tissue  has  great  power  of  growth  and  there  is  no  sharp  line 
of  demarkation  between  the  lipomata  and  the  diffuse  formation  of 
fat  which  may  affect  all  the  fat  organs  or  be  confined  to  the  fat 
tissues  of  one  part  of  the  body,  as  in  adiposis  dolorosa  and  similar 
conditions. 

CHONDROMA;  a  tumor  composed  of  cartilagenous  tissue.  They 
most  commonly  are  found  connected  with  the  skeleton  and  arise 
from  the  perichondrial  or  periosteal  tissue.  They  frequently  are 
multiple,  and  form  hard,  knobby,  irregular  masses.  They  may 
arise  also  in  the  soft  parts.  They  are  gray  in  color,  pearly  and 
translucent.  They  are  extremely  irregular  in  structure  and  the 
normal  types  of  adult  cartilage  are  rarely  found.  The  inter- 
cellular substance,  usually  hyalin,  contains  chondrin.  The  cells 
may  lie  in  definite  capsules,  but  usually  are  devoid  of  these,  and 
in  number  and  form  vary  greatly,  being  round,  spindle  or  stellate. 
Often  large  areas  of  homogeneous  intercellular  substance  are  found 
containing  no  cells,  but  filled  with  spaces  formerly  occupied  by 
them.  Extensive  necroses  are  common  and  the  necrotic  tissue 
becomes  infiltrated  with  lime  salts  forming  large  irregular  masses. 
In  other  cases  bone  is  formed,  either  true  bone  or  an  imperfect 
osteoid  tissue.  Cysts  filled  with  glairy  mucoid  fluid  due  to  soften- 
ing of  the  tumor  tissue  are  not  uncommon.  The  skin  over  the 
tumor  may  ulcerate  from  pressure  and  an  ulcer  with  a  cartilaginous 
base  be  formed.  Such  ulcers,  lacking  the  protection  of  granulation 
tissue,  easily  become  the  atrium  of  infection  and  extensive  necrosis 
of  the  tumor  with  abscess  formation  may  result.  Cartilage  is  much 
more  frequently  found  in  combination  with  other  tissues  than  alone. 
It  seems  easily  to  pass  into  myxomatous  tissue;  there  may  be  much 
fibrous  tissue  and  this  may  be  of  sarcomatous  type.  Combined 


CONNECTIVE  TISSUE  TUMORS  153 

names  such  as  myxo-chondroma,  fibro-chondroma,  chondro-sar- 
coma  are  given  to  signify  such  combinations.  The  chondro- 
mata,  especially  the  mixed  forms,  are  not  benign  tumors.  They 
may  form  immense  tumors,  often  of  rapid  growth,  infiltrating  the 
surrounding  tissue  and  producing  metastases  by  the  blood  stream, 
the  vessels  often  being  penetrated  by  the  tumor  growth. 

OSTEOMA;  a  tumor  formed  of  bone.  The  normal  type  of  bone 
is  repeated  in  the  tumors,  but  there  usually  is  some  irregularity  in 
the  lamellae  and  in  the  corpuscles.  These  tumors  usually  are 
connected  with  bone,  the  tissue  of  the  normal  bone  passing  directly 
into  the  tumor;  or  they  may  be  formed  from  seemingly  inde- 
pendent centres  of  growth  with  a  definite  line  of  separation  between 
the  bone  and  the  tumor.  In  one  variety  of  osteoma,  known  from 
its  hardness  as  the  ivory  osteoma,  the  bone  is  exceedingly  dense, 
contains  few  vessels,  relatively  few  bone  corpuscles  and  takes  a 
high  polish  similar  to  ivory.  The  spongy  osteoma  is  the  opposite 
of  this.  The  osteoma  grows  slowly,  does  not  infiltrate  and  does 
not  form  metastases.  No  sharp  line  can  be  drawn  between  these 
tumors  and  the  various  formations  of  bone  which  take  place  in 
the  body  due  to  a  variety  of  conditions.  Bone  formation  also 
occurs  in  a  number  of  other  tumors  especially  in  the  chondromata 
and  in  sarcomata  arising  from  the  periosteum.  The  true  osteomata 
are  rare  tumors  and  have  no  relation  with  age. 

LEIOMYOMA;  a  tumor  formed  of  non-striated  muscle  tissue  and 
arising  from  this.  The  long  spindle-shaped  cells  with  thin  rod-like 
nuclei  and  the  myoglia  fibrils  characteristic  of  this  tissue  are  re- 
peated in  the  tumor.  The  fibres  are  arranged  in  interlacing  bands 
giving  to  the  cut  surface  a  reticulated  appearance.  The  tumors 
usually  are  smooth  on  the  surface,  easily  separated  from  the  sur- 
rounding tissue  which  often  forms  a  capsule  around  the  tumor,  and 
do  not  produce  metastases.  The  great  frequency  of  these  tumors 
in  the  uterus  makes  the  myoma  one  of  the  most  common  tumor 
forms.  In  the  uterus  they  often  are  multiple  and  may  attain  a 
great  size.  Necrosis  and  hyalin  degeneration  is  common.  Cysts 
may  be  formed  from  the  liquefaction  and  the  absorption  of  the 
degenerated  areas.  Not  infrequently  the  entire  tumor  may  be- 
come calcified  following  necrosis,  and  there  often  is  a  considerable 
admixture  of  fibrous  tissue.  In  certain  of  these  tumors,  often 
described  as  sarcoma  of  the  uterus  and  which  represent  a  malignant 


154  PATHOLOGY 

type  of  the  myoma,  the  growth  is  active,  the  formation  of  myoglia 
fibrils  greatly  diminished  and  the  cells  appear  as  short  spindles 
with  oval  nuclei  rich  in  chromatin.  The  sarcoma-like  growth  may 
appear  in  one  part  of  the  tumor,  the  remainder  having  the  ordinary 
type.  These  tumors  grow  rapidly,  are  infiltrating  and  produce 
metastases.  It  is  obvious  that  such  tumors  bear  the  same  relation 
to  the  ordinary  myoma  that  the  sarcoma  bears  to  the  fibroma. 

HLEMANGIOMA;  a  tumor  composed  largely  of  blood  vessels,  these 
not  merely  serving  the  purpose  of  nutrition,  but  forming  an  integral 
part  of  the  tumor.  The  vessels  are  supported  by  fibrous  tissue. 
There  is  no  differentiation  of  the  vessels  in  the  tumor,  nor  are  their 
walls  distinct  from  the  supporting  tissue.  Two  forms  of  these 
tumors  are  recognized,  the  simple  and  the  cavernous;  in  the  latter, 
most  common  in  the  liver,  the  vessels  form  large  communicating 
spaces.  The  simple  haemangiomata  may  form  large  rapidly  grow- 
ing infiltrating  tumors.  The  congenital  vascular  naevi  are  sepa- 
rated from  the  haemongiomata  in  that  they  represent  chiefly  a 
dilatation  and  elongation  of  the  normal  vessels  of  the  part. 

LYMPHANGIOMA;  a  tumor  representing  the  same  sort  of  formation 
from  the  lymphatic  vessels.  It  may  appear  in  the  form  of  large 
communicating  cystic  spaces  filled  with  lymph.  I  have  seen  two 
such  tumors,  one  in  the  spleen  and  one  in  the  subcutaneous  tissue 
of  the  arm.  In  the  other  form  small  communicating  spaces  are 
found  usually  in  the  midst  of  lymphoid  tissue.  It  is  uncertain  as 
to  what  extent  dilatation  of  pre-existing  vessels  enters  into  their 
formation.  There  is  a  congenital  form  found  in  the  skin  similar 
in  character  to  the  vascular  naevi  and  like  these  due  chiefly  to 
dilatation  of  pre-existing  vessels.  The  most  common  types  of 
these  tumors  are  represented  in  macroglossia  and  macrocheilia. 

ENDOTHELIOMA;  a  great  confusion  exists  in  regard  to  this 
tumor.  In  both  the  haem-  and  the  lymph  angioma  the  growth 
proceeds  from  the  endothelial  cells  which  form  vessels,  the  vascular 
formation  here  being  analogous  to  the  new  formation  of  vessels  in 
granulation  tissue.  In  the  endothelial  tumors  the  growth  of  the 
endothelium  does  not  conform  to  the  physiological  type,  but  is 
excessive,  the  cells  invading  and  growing  into  the  tissue,  often 
forming  whorls  or  growing  in  long  lines.  Usually  places  can  be 
found  in  the  tumor  where  the  endothelial  growth  is  taking  place 
within  vessels  containing  blood  or  lymph.  The  cells  lose  their 


CONNECTIVE  TISSUE  TUMORS  155 

character  as  flat  lining  cells  and  more  closely  resemble  epithelium. 
These  tumors  may  be  of  rapid  growth,  infiltrate  the  surrounding 
tissue  and  form  metastases.  Combinations  between  the  angioma 
and  the  endothelioma  are  not  infrequent.  It  is  a  question  as  to 
whether  the  tumors  arising  from  the  lining  cells  of  the  great  body 
cavities  should  be  placed  with  the  epithelial  or  the  endothelial 
tumors.  Both  the  normal  cells  and  the  cells  of  tumors  arising 
from  them  share  many  of  the  characteristics  of  both  epithelium 
and  endothelium.  The  endothelioma  of  the  dura  arising  from 
cells  histogenetically  related  to  the  peritoneum  or  pleura  form  an 
especial  type  of  tumor.  The  cells  are  small,  flat  and  usually 
arranged  in  connected  masses  lying  in  a  connective  tissue  stroma. 
Often  they  form  concentric  whorls.  Endothelial  growth  from  the 
vessels  seems  also  to  enter  into  the  tumor  formation.  The  con- 
centric whorls  of  cells  may,  after  necrosis,  become  hyaline  or  calci- 
ned forming  sand-like  masses  (psammoma). 

SARCOMA,  a  tumor  arising  from  the  connective  tissue,  in  struc- 
ture departing  from  the  normal  type  of  this  tissue  in  the  abundance 
and  character  of  cells  and  the  relatively  slight  formation  of  inter- 
cellular substance.  The  tumors  have  been  compared  to  the  con- 
nective tissue  of  the  embryo  and  to  granulation  tissue,  but  there 
is  really  little  analogy  either  with  embryonic  or  with  inflammatory 
tissue.  They  may  develop  in  the  connective  tissue  in  any  part 
of  the  body  and  are  most  common  in  such  tissue  as  the  periosteum 
and  connective  tissue  sheaths  and  fasciae.  The  differentiation 
between  the  sarcoma  and  the  epithelial  tumors  may  be  difficult. 
One  of  the  most  characteristic  features  of  the  tissue  from  which 
the  sarcoma  develops  is  the  formation  of  intercellular  fibrils.  This 
is  found  to  a  greater  or  less  extent  in  the  sarcomata.  In  certain 
of  the  very  rapidly  growing  sarcomata  this  characteristic  may  be 
lost  and  all  of  the  energies  of  the  cells  take  the  direction  of  growth. 
In  such  cases  masses  of  cells  may  be  found,  separated  by  an  im- 
perfect stroma  which  partly  represents  the  old  tissue  into  which 
the  tumor  has  penetrated  and  is  in  part  newly  formed  by  the  tumor 
cells.  Fibrils  from  the  stroma  may  penetrate  between  the  cells 
at  the  periphery  of  the  cell  masses  and  the  general  relation  between 
cell  mass  and  stroma  is  much  closer  than  in  the  epithelial  tumors. 
Such  tumors  often  are  called  alveolar  sarcomata.  The  vessels, 
usually  abundant,  may  be  nothing  more  than  mere  fissures  in  the 


156  PATHOLOGY 

tumor  lined  with  endothelium.  Haemorrhage  and  necrosis  are  com- 
mon. Metastases  take  place  chiefly  by  the  blood  stream.  The 
secondary  nodules  may  grow  with  great  rapidity  and  differ  in 
structure  from  the  primary  tumor.  The  cells  sometimes  show  a 
mantel-like  arrangement  along  the  vessels.  Such  tumors  have  been 
called  peritheliomata  or  perithelial  sarcomata,  but  there  is  no 
perithelium  around  the  vessels  from  which  such  a  specifically  named 
tumor  can  develop.  The  sarcomata  vary  greatly  in  malignity. 
No  tumor  shows  such  rapidity  of  growth  or  tendency  to  produce 
metastases  as  do  certain  of  the  sarcomata.  According  to  the 
character  of  the  cells  sarcomata  are  divided  into: 

ROUND  CELL  SARCOMA.  The  cells  have  a  generally  round  shape, 
vary  in  size  in  different  tumors,  often  are  arranged  in  alveoli. 
The  intercellular  substance  usually  is  small  in  amount  and  may 
form  a  reticulum  around  the  cells. 

SPINDLE  CELL  SARCOMA.  The  cells,  of  spindle  shape,  usually 
are  closely  compacted  in  interlacing  bands  in  the  interior  of  which 
are  the  blood  vessels.  A  small  amount  of  intercellular  substance 
and  usually  bands  of  fibrous  tissue  enclosing  the  larger  vessels  are 
found. 

GIANT  CELL  SARCOMA.  Usually  in  combination  with  spindle 
cells,  giant  cells  may  be  found  in  sarcomata.  These  vary  in  size, 
may  be  very  numerous,  and  have  no  especial  characteristics,  are 
round,  elongated  and  irregular  in  outline,  with  the  nuclei  distrib- 
uted irregularly  in  the  cytoplasm.  Such  cells  may  be  found  in 
sarcomata  which  develop  in  the  soft  tissue,  but  more  usually  are 
found  in  those  developing  from  the  bone,  though  there  is  little  ten- 
dency to  bone  formation  in  the  tumor.  These  tumors  are  slow  in 
growth,  and  have  no  tendency  to  metastases.  They  may  disappear 
spontaneously,  and  cysts  may  be  formed  from  their  degeneration. 

Mixed  cell  sarcoma  is  often  used  to  designate  the  tumors  in 
which  the  cells  are  of  an  indeterminate,  character  or  a  mixture  of 
various  forms.  Sarcomata  arising  from  bone  or  from  the  perios- 
teum show  two  types  dependent  upon  the  character  of  the  accom- 
panying bone  formation.  In  the  osteo-sarcoma  there  is  a  varying 
amount  of  bone  formed  which  approaches  or  repeats  the  normal 
type;  in  the  osteoid  sarcoma  the  calcification  may  be  very  im- 
perfect or  absent,  the  bone  being  represented  by  a  hyaline,  often 
reticular  structure  in  which  groups  of  cells  lie. 


CONNECTIVE  TISSUE  TUMORS  157 

MELANOTIC  SARCOMA.  These  tumors,  characterized  by  the 
formation  of  pigment,  deserve  a  definite  place  in  the  classification 
of  tumors.  The  pigment  is  melanin.  It  is  formed,  hi  varying 
amounts,  by  the  tumor  cells  and  varies  in  color  from  brown  to 
intense  black.  In  some  cases  it  is  present  in  such  large  amounts 
that  it  is  excreted  by  the  urine,  giving  this  a  characteristic  color. 
The  tumors  arise  either  in  the  choroid  of  the  eye  or  in  the  skin. 
In  the  latter  place  they  often  develop  from  the  congenital  pig- 
mented  naevi  or  moles  which  have  much  the  same  histological 
structure  as  the  tumor.  The  cells  vary  in  size  and  shape  and 
tend  to  arrangement  in  more  or  less  well-defined  alveoli.  Areas 
of  the  tumor  may  be  entirely  free  from  pigment.  Metastases  occur 
early,  and  are  very  numerous.  The  primary  tumor  may  be  quite 
insignificant  in  comparison  with  the  metastases.  The  melano- 
sarcoma  is  one  of  the  most  malignant  of  tumors. 

NEUROMA.  Tumor-like  masses  may  arise  from  regeneration  of 
the  cut  ends  of  the  nerves  in  an  amputation  stump.  In  the  neuro- 
fibromata  the  nerves  take  no  part  in  the  tumor  formation.  True 
neuromata  are  extremely  rare  and  confined  to  congenital  tumors 
often  of  a  very  malignant  character,  arising  from  the  sympathetic 
system.  These  may  contain  cells  of  the  ganglionic  type  and  nerve 
fibres,  or,  in  the  midst  of  an  indeterminate  sarcoma-like  tissue, 
clusters  of  small  cells  with  sheaves  of  fibrils  in  connection  with 
them  are  found.  Closely  allied  to  the  neuromata  is  the  neuro- 
epithelioma,  a  congenital  tumor  of  the  retina.  This  tumor  is 
composed  of  small  cells  often  circularly  arranged  around  spaces, 
forming  rosettes.  Around  the  space  there  is  a  more  or  less  well- 
differentiated  cuticular  border  through  which  pointed  or  blunt 
processes  of  the  cells  project,  suggesting,  and  probably  imperfectly 
representing,  retinal  rods  and  cones.  The  cells  of  these  congenital 
neuromata  are  very  similar  to  the  early,  undifferentiated  nerve 
cells  in  the  embryo. 

GLIOMA.  Tumors  developing  from  the  neuroglia  show  great 
variation  in  character.  The  cells  of  the  neuroglia,  a  tissue  of 
epiblastic  origin,  occur  as  the  epithelial-like  ependymal  cells  and, 
in  association  with  intercellular  fibrils,  as  the  general  support- 
ing tissue  of  the  central  nervous  system.  The  characteristic 
features  of  these  tumors  is  the  presence  of  neuroglia  fibrils.  Spaces 
lined  with  cells  analogous  to  ependyma  may  be  found.  The 


158  PATHOLOGY 

relation  of  cells  to  fibrils  varies  and  the  cells  may,  in  type  and 
arrangement,  simulate  a  carcinoma.  Haemorrhage  and  necrosis  are 
common.  The  growth,  usually  slow,  may  be  very  irregular.  It 
seems  to  be  influenced  by  the  intracranial  pressure  and  may  in- 
crease rapidly  after  decompression  operations.  The  term  glio- 
sarcoma  has,  without  justification,  been  applied  to  the  very  cellular 
gliomata.  Generally  the  gliomata  are  tumors  of  slow  growth,  not 
sharply  circumscribed  and  do  not  produce  metastases,  being 
malignant  from  situation  only.  They  develop  rarely  outside  the 
central  nervous  system  from  embryonic  displacements  of  neuroglia. 
A  glioma  developing  from  the  neuroglia  of  the  brain  may  project 
from  the  surface  and,  growing  along  the  pia,  simulate  a  tumor 
originating  in  this  membrane. 

RHABDOMYOMA,  a  tumor  always  of  embryonic  origin  whether 
congenital  or  not,  characterized  by  the  presence  of  imperfect  forms 
of  striated  muscle  tissue.  Two  chief  forms  of  this  are  seen :  spindle 
cells,  sometimes  joined,  with  characteristic  striation  of  the  cyto- 
plasm, and  large,  irregular  vacuolated  cells  with  the  sarcous  ele- 
ments appearing  as  pairs  or  rows  of  dots.  The  typical  embryonic 
hollow  cylinders  with  exterior  striation  are  not  found.  These 
tumors  may  appear  in  the  heart  or  in  some  relation  to  the  genito- 
urinary system.  In  the  latter  situation  there  is  always  an  ad- 
mixture of  other  sorts  of  tissue.  The  rhabdomyomata  of  the  heart 
usually  are  accompanied  by  some  form  of  malformation  of  the 
central  nervous  system. 


TUMORS  OF  THE  BLOOD 

The  pathology  of  this  system  is  complicated  and  difficult  of 
clear  comprehension.  This  is  due  in  part  to  the  fact  that  the 
embryonic  condition  persists  in  adult  life.  Regeneration  takes 
place,  not  by  multiplication  of  cells  which  have  undergone  a  complete 
differentiation,  but  by  growth  of  a  persistent  embryonic  tissue,  the 
cells  becoming  differentiated  in  the  process  of  their  development. 
The  tissue  has  great  power  of  growth,  this  being  shown  not  only  in 
the  formation  of  new  cells  in  the  numerous  foci  of  the  tissue  which 
normally  are  present,  but  by  the  fact  that  new  foci  easily  arise. 
Under  normal  relations  the  undifferentiated  cells  remain  at  the  foci 
of  formation  (bone  marrow  and  lymph  nodes),  but  in  pathological 
conditions  these  undifferentiated  cells  also  may  pass  into  the  circu- 
lation. The  tumors  have  become  confused  with  the  hyperplasia  of 
tissue,  the  result  of  reaction  to  injury,  which  may  greatly  resemble 
tumor  formation  and  in  which  unusual  cell  forms  appear.  Bearing 
this  in  mind,  we  still  can  single  out  from  the  confusion  of  tissue 
changes  and  the  equally  confused  nomenclature  certain  entities. 

LYMPHOMA,  a  tumor  of  the  lymphoid  system  formed  of  lym- 
phoid  cells,  but  without  the  tissue  structure  of  the  lymph  node. 
It  is  uncertain  whether  or  not  multiplication  ever  takes  place  from 
the  small  cells  which  we  are  accustomed  to  think  of  as  the  repre- 
sentative cells  of  the  lymphoid  system.  The  cells  which  compose 
the  main  mass  of  the  tumors  conform  closely  in  size  and  structure 
to  the  cell  type  as  found  in  the  germinal  centres  of  the  lymph  nodes. 
The  tumors  may  appear  primarily  in  any  part  of  the  lymphoid 
system,  the  growth  being  characterized  by  periods  of  inactivity 
and  periods  of  great  rapidity  of  growth.  At  times  the  tumors 
seem  to  arise  from  a  single  focus  with  a  rapid  secondary  involve- 
ment of  other  similar  tissue;  at  others  the  tumor  formation  may 
appear  as  a  system  disease,  similar  to  neuro-fibroma,  in  a  number 
of  foci  simultaneously.  Metastases  are  formed  in  great  numbers  by 
both  the  blood  and  the  lymphatics  and  may  appear  in  all  the  organs 
of  the  body.  Haemorrhages  are  very  frequent  in  the  metastases, 
less  frequent  in  the  primary  tumors. 

159 


160  PATHOLOGY 

MYELOMA,  a  tumor  arising  in  the  bone  marrow.  It  is  impos- 
sible to  say  which  one  of  the  cell  series  in  the  marrow  constitutes 
the  mother  cell.  The  cell  outline  is  sharp,  the  cytoplasm  dense 
without  definite  granulation,  often  strongly  basophilic,  in  which 
case  the  cells  somewhat  resemble  plasma  cells,  or  it  may  be  neutro- 
philic  or  even  acidophilic.  The  nuclei  are  large,  very  distinct,  and 
in  most  cases  contain  a  large,  definite,  acidophilic  nucleolus.  The 
tumor  is  destructive  in  growth,  and  there  is  little  or  no  accom- 
panying periosteal  bone  formation.  The  growth  varies  at  different 
periods,  at  times  apparently  ceasing,  and  the  tumor  may  even 
retrogress  in  size,  these  periods  being  followed  by  very  active 
growth.  The  tumors  may  be  single  or  multiple.  Metastases  are 
infrequent,  but  may  occur  in  the  lymph  nodes  and  elsewhere. 
Bence- Jones  albumosuria  has  been  found  very  generally  in  the 
urine  in  cases  of  myeloma. 

CHLOROMA,  a  peculiar  and  rare  tumor  arising  most  usually  in 
the  bones  of  the  face  and  orbit  and  characterized  by  the  presence 
of  green  or  greenish-yellow  pigment  which  fades  on  exposure  to 
the  air.  The  cells  are  indefinite  in  character,  resembling  large 
lymphocytes. 

LEUKEMIA.  It  is  most  convenient  to  consider  this  in  connec- 
tion with  the  tumors  of  the  blood  system.  The  name  should  be 
regarded  as  a  clinical  term  to  describe  a  condition  in  which  large 
numbers  of  white  cells  are  present  in  the  blood.  These  may  be  so 
numerous  that  the  blood  becomes  purplish  or  lilac  in  color.  Two 
forms  of  leukemia  are  recognized:  one,  myelogenous  leukemia,  in 
which  the  excess  of  cells  are  of  the  myelocyte  type;  the  other, 
lymphatic  leukemia,  in  which  the  cells  are  of  the  lymphoid  cell 
type.  In  many  cases  these  types  are  not  pure  and  the  name 
mixed-cell  leukemia  is  used.  In  all  cases,  but  especially  in  the 
myelogenous  leukemia,  there  is  an  enormous  excess  in  the  amount 
of  blood.  All  the  veins  are  dilated  and  the  greatly  increased 
weight  of  the  organs  (weights  of  liver  and  spleen  up  to  5000  grams 
each  are  not  uncommon)  is  due  mainly  to  the  amount  of  blood 
contained  in  them.  Neither  hypertrophy  nor  dilatation  of  the 
heart  accompanies  the  condition. 

LYMPHATIC  LEUKEMIA.  In  cases  of  lymphoma  the  tumor  cells 
easily  find  access  to  the  blood  either  directly  or  through  the  lym- 
phatics. In  autopsies  on  cases  of  lymphoma  the  cells  often  are 


TUMORS  OF  THE  BLOOD  161 

present  in  the  vessels  of  internal  organs  in  considerable  numbers. 
It  is  possible  that  these  cells,  the  conditions  being  unfavorable, 
are  destroyed  in  the  blood.  The  lymphatic  leukemia  represents 
those  cases  of  lymphoma,  in  which,  along  with  other  metastases, 
there  is  metastasis  in  the  blood.  The  extraneous  tumor  cells 
entering  into  the  blood  find  conditions  favorable  not  only  for 
preservation,  but  for  growth.  The  cell  forms  in  the  blood,  es- 
pecially hi  the  more  acute  cases,  may  repeat  those  found  in  the 
tumors  or  there  may  be  a  further  differentiation  with  the  fully 
differentiated  lymphoid  cell  chiefly  represented.  In  the  more 
chronic  cases  the  metastases  are  less  numerous,  larger  in  size,  and 
are  especially  marked  in  the  spleen.  This  may  be  greatly  enlarged 
and  filled  with  grayish  tumor  masses.  The  cells  in  the  blood  are 
chiefly  of  the  small  differentiated  type. 

MYELOGENOUS  LEUKEMIA.  This  is  due  to  a  tumor  formation 
in  the  myelogenous  tissue  analogous  to  that  taking  place  in  the 
lymphoid  tissue  in  lymphatic  leukemia.  The  cell  forms  repre- 
sented in  the  blood  are  premature  or  mature  myelocytes.  The 
fat  in  the  marrow  disappears  and  the  marrow  of  all  the  bones  is 
filled  with  an  opaque,  gray-red  mass  of  soft  tissue  in  which  the 
medullary  spicules  of  bone  may  be  absent.  The  marrow  in  all  of 
the  bones  is  affected,  so  that  the  condition  is  to  be  regarded  as  a 
systemic  tumor.  Metastases  of  myelogenous  tissue  are  found,  but 
are  not  so  definite  as  those  in  lymphoma.  The  myelogenous  cells 
not  only  pass  from  the  marrow  into  the  blood,  but  multiply  there, 
nuclear  figures  being  found  in  the  circulating  cells.  There  are  no 
cases  of  the  tumor  formation  hi  the  marrow  without  the  metastases 
into  the  blood.  There  is  no  distinct  name  for  this  tumor  forma- 
tion. The  name  myeloma  refers  to  a  very  different  process  in 
which  there  are  no  blood  changes. 

In  both  the  lymphoid  and  the  myelogenous  forms  of  leukemia 
there  may  be  an  admixture  of  the  cell  types,  but  one  type  pre- 
dominates. It  is  natural  that  there  should  be  some  admixture  in 
cell  proliferation  in  two  systems  so  closely  related  as  the  myelog- 
enous and  lymphoid  tissues.  The  bone  marrow  under  normal 
conditions  contains  lymphoid  cells  and  in  lymphatic  leukemia  may 
be  almost  as  fully  involved  in  the  tumor  formation  as  it  is  in  the 
myelogenous  forms. 


EPITHELIAL  TUMORS 

The  epithelial  tissue  in  its  power  of  growth,  regeneration  and 
function  is  the  most  active  of  all  the  tissues.  With  the  exception 
of  the  nervous  system  the  epithelium  wherever  found  is  in  relation 
with  surfaces  which,  except  in  the  ductless  glands,  are  in  com- 
munication with  the  exterior.  The  various  sorts  of  epithelium 
have  great  differentiation  in  function  which  to  a  great  extent  is 
expressed  in  their  morphology.  There  is  everywhere  a  close  rela- 
tion between  epithelium  and  connective  tissue,  proliferating  epi- 
thelium being  accompanied  by  a  new  growth  of  blood  vessels  and 
a  supporting  stroma  of  connective  tissue.  This  close  relation  is 
expressed  in  the  fibro-epithelial  tumors,  in  which  it  often  is  im- 
possible to  decide  which  of  the  two  tissues  predominates.  The 
structural  differentiation  of  the  different  epithelia  is  to  a  consider- 
able extent  preserved  in  the  tumors.  There  are  no  epithelial 
tumors  in  which  the  cells  in  morphology  and  mode  of  growth  show 
such  complete  absence  of  differentiation  as  is  seen  in  certain  of  the 
sarcomata.  The  essential  elements  in  the  epithelial  tumors  are 
the  epithelial  cells.  The  stroma  coming  from  the  adjoining  tissue 
is  secondary.  According  to  the  relation  of  the  cells  and  stroma 
the  epithelial  tumors  can  be  divided  into  two  great  classes,  the 
adenomata  and  the  carcinomata. 

ADENOMA.  In  the  adenoma  the  cells  have  the  same  relation  to 
the  stroma  as  is  found  in  normal  glandular  tissue;  there  are  alveoli 
lined  with  epithetial  cells  separated  from  the  connective  tissue  by 
a  basement  membrane.  In  the  tumor  this  arrangement  is  pre- 
served, the  cells  retaining  their  relations  and  pushing  out  the 
separating  membrane  before  them.  In  certain  glands,  in  addition 
to  a  membrana  propria,  there  is  an  enveloping  layer  of  smooth 
muscle  fibres  and  this  also  enters  into  the  structure  of  the  adenoma. 
In  the  formation  of  the  tumor  the  cells  at  some  point  of  the  wall  of 
an  epithelial-lined  cavity  begin  to  proliferate  forming  a  small  mass 
into  which  the  blood  vessels  from  the  stroma  grow.  With  the 

162 


EPITHELIAL  TUMORS  163 

continuation  of  the  growth  and  with  the  formation  of  other  centres 
of  growth  into  which  secondary  papillae  project,  most  complicated 
structures  arise.  The  cavity  in  which  the  growth  started  enlarges 
with  the  growth  of  the  branching  masses  within  it.  In  most 
adenomata  both  forms  of  growth  are  seen,  but  one  or  the  other 
usually  predominates.  When  the  papillary  form  extends  to  such 
a  surface  as  the  peritoneum  portions  of  the  papillae  are  easily  broken 
off  and  form  new  attachments  and  new  foci  of  growth.  The  cells 
lining  the  alveoli  of  an  adenoma  may  not  lose  their  secretory  power 
and  the  accumulation  of  the  secretion  leads  to  the  formation  of 
cysts.  The  name  adeno-cystoma  or  papilliferous  adeno-cystoma 
applies  to  these  conditions.  It  is  obvious  that  there  is  no  essential 
difference  between  any  epithelial-lined  cavities  or  canals  and  the 
alveoli  of  a  gland;  in  such  cavities  and  canals  papillary  epithelial 
growths  may  be  formed.  The  character  of  the  papillae  may  vary, 
in  one  case  being  extremely  long  and  thin  with  many  branches,  in 
others  being  shorter  and  broader.  The  character  of  the  papillary 
growth  seems  to  depend  upon  the  character  of  the  epithelium  or 
possibly  upon  the  contents  of  the  cavity.  In  certain  places,  as 
in  the  bladder,  such  papillary  tumors  are  malignant.  In  other 
cases  true  carcinomata  develop  at  the  base  of  the  tumor,  the  epi- 
thelium growing  into  the  surrounding  tissue. 

CARCINOMA  is  an  epithelial  tumor  in  which  the  character  of  the 
epithelial  growth  is  atypical  and  the  resulting  tumor  structure  has 
no  analogy  with  normal  epithelial  organs.  The  essential  char- 
acteristic of  the  carcinoma  is  that  the  cells  have  the  capacity  of 
invading  the  tissue  growing  out  in  it  and  penetrating  the  tissue 
spaces  and  lymphatics.  They  do  not  retain  then-  normal  rela- 
tions with  each  other  nor  with  the  stroma.  They  often,  to  a 
great  extent,  retain  the  morphological  characteristics  of  the  epi- 
thelium from  which  the  growth  arises,  but  may  be  very  dissimilar 
and  rarely  show  any  indication  of  function.  Usually  they  are 
larger  than  the  corresponding  normal  cells,  have  an  abundant 
compact  cytoplasm,  and  one  or  more  large  vesicular  nuclei  rich 
in  chromatin.  It  is  natural  that  such  an  epithelial  tumor,  with  an 
unlimited  power  of  growth  of  the  constitutent  cells,  and  capacity 
for  invading  the  adjoining  tissues,  should  form  the  prototype 
of  a  malignant  tumor.  The  carcinoma  extends  locally  by  infiltra- 
tion, secondary  nodules  being  formed  in  the  vicinity  by  ingrowth 


164  PATHOLOGY 

of  cells  or  their  conveyance  along  the  lymph  spaces.  Metastases 
arise  from  cells  conveyed  to  other  parts  by  the  blood  or  lymph 
circulation  and  there  is  marked  tendency  to  recurrence  after  re- 
moval. The  epithelial  cells  of  a  carcinoma  in  the  beginning  form 
a  single  connected  mass  penetrating  the  tissue.  Single  cells  may 
become  detached  and  form  new  centres  of  growth.  Section  of  the 
tumor  always  shows  masses  of  epithelium  surrounded  by  con- 
nective tissue  and  blood  vessels.  The  separation  between  the 
stroma  and  epithelial  masses  is  sharp.  The  shape  and  direction 
of  the  epithelial  masses  depend  to  some  extent  upon  the  course 
of  the  lymphatics.  An  epidermoid  carcinoma  near  the  surface 
shows  perpendicular  extensions,  but  lower  down  they  are  more 
horizontal.  The  size  of  the  alveoli  varies.  They  may  be  very 
large,  or  composed  of  but  a  single  line  of  epithelial  cells.  The 
growth  of  the  tumor  is  most  active  in  the  periphery.  The  active 
growth  of  the  cells  in  the  periphery  may  interfere  with  the  nutrition 
of  the  centre  of  the  tumor  by  compression  of  the  vessels  so  that 
active  peripheral  growth  may  be  accompanied  by  atrophy,  necrosis 
and  contraction  of  the  centre.  Nuclear  figures  are  abundant  and 
often  show  atypical  forms.  Ulceration  in  carcinoma  is  common. 
When  the  growth  reaches  the  surface  the  covering  epithelium  is 
deprived  of  its  nutrition,  undergoes  necrosis  sometimes  with  pre- 
ceding vesicle  formation  and  is  cast  off.  In  such  ulcers,  there  may 
be  formation  of  granulation  tissue  which  is  invaded  secondarily 
by  the  epithelial  cell  masses.  The  tumors  may  vary  greatly  in 
character,  and  such  variations  have  received  different  names. 
The  ordinary  type,  showing  the  usual  relation  between  alveoli  and 
stroma,  is  called  carcinoma  simplex.  Scirrhus  is  used  to  describe 
those  forms  in  which  the  stroma  is  abundant,  firm,  and  the  whole 
tumor  shows  evidences  of  contraction.  In  medullary  carcinoma 
the  alveoli  are  relatively  large  and  the  stroma  small  in  amount. 
The  medullary  and  scirrhus  types  may  be  present  in  the  same  tumor. 
Ulceration  is  always  a  marked  feature  in  carcinomata  of  the  ali- 
mentary canal.  The  general  type  of  such  tumors  is  a  central,  deep, 
more  or  less  clean  ulcer  surrounded  by  an  elevated  wall  of  growing 
tumor.  The  growth  is  often  encircling  because  of  extension  along 
the  lymphatics.  Stenosis  of  the  canal  results,  due  both  to  con- 
traction of  the  stroma  and  to  the  projecting  tumor  masses.  Tran- 
sition forms  between  the  adenoma  and  carcinoma  are  not  infre- 


EPITHELIAL  TUMORS  165 

quent.  In  a  tumor  starting  as  an  adenoma,  the  typical  epithelial 
growth  may  become  changed  into  the  atypical  growth  of  the  car- 
cinoma. In  the  same  way  in  the  carcinoma,  a  tendency  to  the 
normal  type  of  epithelial  growth  is  often  seen  in  the  arrangement 
within  the  alveoli  of  groups  of  cells  around  small  spaces  repre- 
senting lumina.  The  following  classes  of  carcinoma  may  be  dis- 
tinguished, depending  upon  the  type  of  epithelial  tissue  from  which 
the  tumor  has  arisen. 

EPIDERMOID  CARCINOMA  arises  from  squamous  epithelium.  It  is 
characterized  by  an  invading  growth  of  the  epithelium  and  a  tend- 
ency to  the  formation  of  concentric  masses  of  keratinized  cells  in  the 
interior  of  the  alveoli  called  pearls.  Each  mass  of  epithelium  to  a 
certain  extent  repeats  the  structure  of  the  epidermis.  On  the 
outside  is  a  layer  of  epithelium  similar  in  character  to  the  mal- 
pighian  layer.  The  nuclei  are  oval  with  the  long  axis  perpendicular 
to  the  surface,  and  with  abundant  chromatin;  nuclear  figures  are 
numerous.  Next  to  this  layer  come  several  layers  showing  a 
marked  development  of  the  intercellular  bridges  followed  by  a 
central  mass  of  keratinized  cells.  The  degree  of  keratinization 
varies  greatly  in  the  different  tumors.  The  tissue  affected  being 
open  to  observation,  the  development  and  growth  of  this  tumor 
has  been  closely  followed.  The  tumor  often  is  preceded  by  an 
active  growth  of  epithelium  and  an  increased  thickness  of  the 
horny  layer  forming  slightly  projecting  masses.  Such  a  condition 
may  exist  for  some  time  before  the  strictly  carcinomatous  growth 
begins,  this  often  being  preceded  by  an  intense  infiltration  of  the 
corium  with  lymphoid  cells.  The  growth,  as  a  rule,  is  less  rapid 
than  that  of  the  glandular  carcinoma,  metastases  occur  less  early 
and  are  usually  confined  to  the  lymph  nodes.  A  variety  of  this 
carcinoma  is  known  as  the  baso-cellular  type  from  the  erroneous 
idea  that  the  tumor  arises  from  the  basal  epithelial  cells  of  the 
epidermis.  The  cells  in  this  are  small,  often  cylindrical,  closely 
packed  and  of  the  same  character  throughout.  There  are  no  prickle 
cells  and  there  is  no  formation  of  epithelial  pearls.  The  alveoli  are 
large,  and  the  interlacing  network  which  they  form  is  very  evident. 
Epithelial  fibrils  in  great  numbers  may  be  present  in  the  alveoli. 
These  tumors  are  of  very  slow  growth,  there  is  little  tendency  to 
invade,  they  do  not  form  metastases,  and  they  may  be  multiple. 
With  necrosis  and  destruction  of  the  overlying  epidermis,  a  very 


i 66  PATHOLOGY 

chronic,  slowly  extending,  superficial  ulcer  (rodent  ulcer)  results.  It 
has  been  supposed  from  the  abundant  fibril  formation  that  the  tumor 
has  its  origin  in  the  hair  follicles.  It  is  difficult  to  believe  this  in 
view  of  the  fact  that  the  rapidity  of  growth  of  a  tumor  is  largely 
influenced  by  the  growth  capacity  of  the  tissue  from  which  it  arises 
and  there  are  few  tissues  in  the  body  with  such  growth  capacity 
as  is  shown  by  the  hair  follicles. 

GLANDULAR  CARCINOMA,  a  carcinoma  having  its  origin  in 
glandular  epithelium,  the  type  of  the  tumor  appearing  in  carcinoma 
of  the  mamma.  This  tumor  is  so  common  and  so  frequently 
investigated  that  general  descriptions  of  carcinoma  are,  in 
large  measure,  based  upon  it.  The  character  of  the  tumor 
varies  greatly. 

CYLINDRICAL  CELL  CARCINOMA.  Carcinomata  which  develop 
from  cylindrical  epithelial  cells  retain  this  cell  type  to  a  remarkable 
degree.  These  cells  tend  to  grow  in  contact  with  the  long  axes 
parallel.  The  alveoli  are  very  generally  hollow,  or  if  they  contain 
cells  in  excess  of  those  lining  the  walls,  these  are  disposed  in  the 
interior  in  rows.  Not  infrequently  there  may  be  several  layers  of 
the  lining  cells.  In  the  more  rapidly  growing  parts  of  the  tumor, 
the  cells  may  lose  the  definite  cylindrical  type,  becoming  cuboidal 
or  irregular  and  growing  in  the  alveoli  in  solid  masses.  The  pre- 
vailing arrangement  of  the  cells  around  a  lumen  resembles  the  cell 
arrangement  in  adenoma  and  these  tumors  have  been  called  adeno- 
carcinomata,  but  the  resemblance  to  the  adenoma  does  not  go 
further  than  the  cell  arrangement.  There  is  no  definite  limiting 
membrane  separating  the  epithelium  from  the  stroma,  and  the 
tumor  in  all  other  particulars  resembles  the  carcinoma. 

Another  form  of  carcinoma  called  colloid  or,  more  properly, 
mucoid  carcinoma  results  from  the  abundant  formation  of  mucin, 
both  in  the  tumor  cells  and  the  stroma,  which  gives  to  the  tumor 
a  transparent,  gelatinous  appearance.  Formerly  they  often  were 
called  alveolar  carcinomata,  because  the  alveolar  structure  was 
more  prominent  in  them.  The  cells  are  found  in  all  stages  of 
mucoid  degeneration  and  often  alveoli  filled  with  dense  mucus 
result  from  the  total  transformation  of  the  cells.  The  colloid 
carcinoma  most  frequently  originates  from  mucous  membranes. 

CHORIO-EPITHELIOMA,  a  tumor  of  peculiar  type  which  in  its 
typical  form  develops  from  the  villi  of  the  chorion.  The  tumor 


EPITHELIAL  TUMORS  167 

has  a  relation  to  the  formation  of  the  uterine  or  hydatidiform  mole 
and  in  about  half  the  cases  is  preceded  by  this  condition.  In  the 
mole  formation,  the  villi  become  enormously  enlarged  by  the 
accumulation  of  fluid,  often  with  an  excess  of  mucus,  in  the  con- 
nective tissue.  With  this  there  is  almost  invariably  considerable 
growth  of  the  covering  epithelium.  In  the  chorio-epithelioma 
both  layers  of  the  covering  epithelium  proliferate.  The  syncytial 
layerHs  a  covering  protoplasmic  mass,  the  cytoplasm  dense,  the 
nuclei  placed  at  intervals.  The  layer  often  projects  in  the  form 
of  round  or  polypoid  masses  containing  great  numbers  of  nuclei. 
The  Langerhans'  cell  layer  below  this  is  formed  of  cuboidal  cells 
with  clear  cytoplasm  and  large  vesicular  nuclei  and  numerous 
nuclear  figures.  There  is  an  irregularly  disposed  vascular  stroma, 
but  the  cell  masses  for  the  most  part  grow  freely  in  the  blood 
sinuses  without  any  stroma.  The  tumor  has  the  power  of  invading 
and  destroying  tissue,  the  growth  being  chiefly  within  vessels  and 
the  metastases  principally  in  the  lung.  Tumors  in  all  respects 
similar  in  character  may  appear  in  other  parts  of  the  body  as  in 
the  testicle,  ovary,  vagina,  liver  and  peritoneum.  In  the  ovary 
and  testicle  they  usually  are  found  in  combination  with  teratomata 
and  it  has  been  assumed  that  a  chorion  has  been  produced  in  the 
teratoma  in  which  the  tumor  has  developed.  The  essential  feature 
of  the  tumor  is  the  peculiar  form  of  epithelial  growth  and  it  is  not 
impossible  that  this  may  occur  in  other  forms  of  epithelium. 

HYPERNEPHROMA.  Tumors  derived  from  the  adrenal  glands 
(hypernephron)  usually  are  considered  together.  They  are  epi- 
thelial tumors  and  the  adenomatous,  papillary  and  carcinomatous 
forms  may  be  represented.  In  the  simplest  form  they  appear  as 
small  circumscribed  masses  in  the  cortex,  or  in  the  capsule  of  the 
adrenal  gland,  or  in  similar  positions  in  the  kidney.  The  cells  are 
large,  pale,  vacuolated,  and  contain  fat  and  glycogen.  They 
resemble  most  the  cells  of  the  glomerular  layer  of  the  adrenal. 
The  tumors  which  are  more  atypical  in  the  character  and  in  the 
arrangement  of  the  cells  form  large  masses  usually  developing 
within  the  kidney,  with  a  marked  tendency  to  haemorrhage  and 
to  invasion  of  blood  vessels,  the  organ  becoming  in  great  measure 
destroyed  by  the  growth.  The  papillary  growth  is  often  pro- 
nounced, the  papillae  extremely  long,  thin  and  without  branching. 
The  metastases  are  numerous  and  occur  chiefly  in  the  lung, 


i68  PATHOLOGY 

although  they  may  appear  in  any  part  ol  the  body.  In  the  lung 
there  often  is  a  secondary  extension  of  the  metastatic  growth  into 
the  lymphatics  which  can  become  filled  with  the  tumor.  Tumors 
of  similar  character  and  evidently  originating  in  embryonic  adrenal 
inclusions  may  develop  on  the  lower  border  of  or  within  the  liver. 


TERATOID   TUMORS 

These  form  a  class  of  tumors  of  varying  stricture,  in  some  cases 
simple,  in  others  of  great  complexity,  differing  radically  from  the 
tissue  in  which  they  arise.  This  class  of  tumors  has  some  relation 
to  monster  formations  and  more  than  any  other  tumors  can  be 
referred  to  errors  in  development  resulting  in  a  misplacement  of 
embryonic  tissue. 

THE  EPIDERMOID  CYST  is  the  simplest  of  these  tumors.  This 
is  a  small  cystic  tumor  which  is  most  frequent  in  the  scalp,  but  may 
appear  in  the  cutis  in  other  parts  of  the  body.  It  is  lined  with  a 
simple,  thin  layer  of  epidermis  without  papillae  and  without  any 
epidermic  structures,  and  is  filled  with  a  mass  of  butter  consistency, 
containing  fat,  epidermic  scales  and  cholesterin.  It  is  due  to 
separation  and  inclusion  of  epidermis  during  the  development  of 
the  skin.  THE  CHOLESTEATOMA  represents  one  form  of  this  tumor. 
Like  the  epidermoid,  it  is  composed  of  a  cyst  wall  with  an  epi- 
dermic covering  and  contains  a  mass  composed  of  horny  adherent 
epidermic  scales  and  often  cholesterin.  The  contents  have  a  peculiar 
pearly  lustre.  The  most  common  situation  of  this  tumor  is  at  the 
base  of  the  brain.  Its  presence  here  is  to  be  referred  to  inclusion  of 
epidermic  cells  at  the  period  of  closure  of  the  medullary  canal. 

DERMOID  CYSTS.  These  are  cystic  tumors  in  whose  walls  all 
the  epidermic  structures  are  found.  In  the  contents  of  the  cysts 
hair  and  sebaceous  material  may  be  found.  These  tumors  occur 
by  preference  in  relation  to  the  anterior  middle  line  of  the  body, 
especially  in  regions  where  the  embryological  development  is  com- 
plex. The  tumor  may  be  multilocular,  secondary  cysts  being 
formed  from  the  primary.  Unlike  the  epidermoid,  the  connective 
tissue  on  which  the  epithelium  rests  forms  a  true  part  of  the  tumor. 
Here  the  inclusion  is  not  of  epidermis  alone,  but  of  the  embryonic 
true  skin.  Cases  are  recorded  in  which  epidermoid  carcinoma  has 
developed  from  the  wall  of  such  a  cyst. 

THE  TERATOMATA  are  still  more  complicated,  and  often  are  very 
highly  developed  tumors.  In  these,  tissues  arising  from  the  three 
layers  of  the  embryo  always  are  found,  and  in  some  practically  all 

169 


170  PATHOLOGY 

the  tissues  of  the  body  may  be  represented.  They  always  are,  to 
greater  or  less  extent,  cystic  and  not  infrequently  are  multiple. 
Their  most  common  situation  is  in  the  ovary.  The  two  types 
found  here  are:  (i)  a  single  cyst  containing  hair  and  sebaceous 
material  with  an  elevation  at  one  part  of  the  wall  to  which  teeth 
are  attached.  The  teeth  may  be  numerous  representing  all  forms 
and  may  also  be  found  in  the  cyst  contents.  They  are  attached 
to  a  bone  structure  often  resembling  a  part  of  the  jaw  and,  in  the 
soft  tissue  in  the  vicinity,  small  cysts  or  canals  lined  with  cylin- 
drical epithelium  will  be  found;  (2)  a  tumor,  often  of  rapid  growth, 
more  solid  in  structure,  but  containing  a  number  of  small  cysts.  Not 
only  do  we  find  in  these  tumors  many  different  tissues,  but  definite 
organs  may  also  be  formed.  Nervous  tissue  in  the  form  of  neuroglia 
is  very  common  and  sympathetic  ganglia  with  nerves,  cerebellar 
and  cerebral  tissue  may  be  found.  Some  of  the  cysts  evidently 
are  of  ependymal  origin  lined  with  ependymal  cells  and  surrounded 
by  neuroglia.  Canals  representing  the  intestine  with  mucous, 
sub-mucous,  and  muscular  layers  are  found.  The  teratomata  also 
appear  in  the  testicle,  in  the  peritoneal  cavity,  in  the  sacrococcygeal 
region  and  within  the  skull.  They  may  be  congenital  or  develop 
later  in  life,  often  at  the  time  of  puberty.  Metastases  are  seen 
infrequently.  In  these  only  certain  of  the  tissues  represented  in 
the  tumor  appear.  There  have  been  a  number  of  theories  in 
explanation  of  these  tumors:  (i)  that  they  are  due  to  the  inclusion 
of  an  undeveloped  embryo  within  the  tissues  of  a  developing 
embryo;  (2)  that  they  are  due  to  inclusion  of  polar  bodies;  (3)  that 
they  are  due  to  the  inclusion  of  blastomeres  at  an  early  period  of 
segmentation  when  these  cells  still  possess  the  potentialities  of 
complete  development. 

MIXED  TUMORS.  More  or  less  related  to  the  teratomata  is  the 
class  of  mixed  tumors.  In  these,  various  tissues  are  represented, 
but  there  is  never  the  coordination  among  them  leading  to  typical 
structures  such  as  is  seen  in  the  teratomata.  Their  origin  is  to  be 
referred  to  the  inclusion  of  embryonic  structures.  In  certain  of 
them  the  tissue  of  the  tumor  remains  of  embryonic  character,  and 
to  these  the  name  embryoma  might  fitly  be  applied.  They  differ 
also  according  to  the  situation  in  which  they  appear. 

Mixed  tumor  of  the  kidney  always  is  congenital  or  appears  early 
in  life,  usually  before  the  fifth  year.  It  is  a  tumor  of  the  kidney 


TERATOID  TUMORS  171 

and  is  enclosed  in  the  capsule  of  the  organ.  It  often  grows  rapidly 
and  may  produce  metastases.  The  structure  is  very  characteristic. 
It  consists  of  a  stroma  of  cellular  fibrous  tissue  which  may  contain 
striated  muscle  fibres  and  masses  of  cells  of  indifferent  embryonic 
character.  Within  these  masses  are  gland-like  tubules  seemingly 
formed  by  the  cells.  In  other  places  there  is  not  such  a  definite 
gland-like  formation,  but  cell  rosettes  somewhat  resembling  the 
rosettes  in  the  neuro-epithelioma  of  the  retina  are  seen.  In  a  few 
cases  small  cysts  lined  with  epidermis  and  forming  keratinized 
pearls  have  been  described.  These  tumors  generally  are  regarded 
as  due  to  the  inclusion  in  the  kidney  of  a  part  of  the  wolffian  body, 
or  a  tissue  even  more  primitive  than  this. 

Mixed  tumor  of  the  parotid  gland  is  a  much  more  common  type 
of  mixed  tumor  which  occurs  in  the  region  of  the  parotid  gland. 
These  tumors  are  smooth  on  the  surface,  often  greatly  lobulated, 
the  lobules  extending  deeply  into  the  gland,  thus  presenting  diffi- 
culties of  removal.  On  section  they  contain  islands  of  hyalin 
character,  often  islands  of  osteoid  tissue  or  true  bone,  myxomatous 
tissue,  and  peculiar  masses  and  strands  of  cells  which  extend  in  all 
directions.  Cysts  lined  with  these  cells  often  occur.  There  has 
been  much  dispute  as  to  the  nature  of  the  cells  in  the  strands, 
whether  epithelial  or  endothelial  in  character.  The  latter  seems 
more  probable.  Similar  tumors  are  found  rarely  in  the  sub- 
maxillary  region  and  also  are  referred  to  an  inclusion  of  embryonic 

tissues. 

A  CASE  OF  EPIDERMOID  CARCINOMA  OF  THE  Ln> 

Male,  white,  age  sixty-three.  For  several  months  past  has  had  a 
sore  on  the  lip.  Two  years  ago  a  hardened  scale  appeared  which  he 
picked  off.  This  was  repeated  several  times,  a  sore  finally  developing 
at  the  point.  Has  smoked  a  pipe  for  years. 

Received  for  examination  a  V-shaped  piece  of  tissue  3  by  2.5  by  i  cm. 
together  with  some  loose  tissue  containing  lymph  nodes.  The  larger 
piece  of  lip  tissue  shows  on  one  side  shaven  skin,  on  the  other  smooth, 
pale  mucous  membrane.  In  the  middle  of  the  upper  surface  at  the 
junction  of  skin  and  mucous  membrane,  is  a  small  superficial  ulcer, 
irregular  in  shape,  6  by  5  cm.  The  tissue  beneath  and  in  the  vicinity 
of  the  ulcer  is  indurated  and  immovable.  On  section  through  the  ulcer 
a  gray,  rather  opaque  tissue  continuous  laterally  with  the  epidermis  is 
found  beneath  it.  This  tissue  is  from  i  to  2  mm.  in  thickness,  the  lower 
border  not  being  distinct. 


172  PATHOLOGY 

One  of  the  lymph  nodes  shows  on  section  a  small  opaque  grayish  area 
about  2  mm.  in  diameter,  situated  in  the  periphery.  The  two  other 
small  nodes  are  normal.  The  rather  loose  reddish  tissue  is  found  to  be 
submaxillary  gland. 

A  CASE  OF  CARCINOMA  OF  THE  (ESOPHAGUS 

Anatomical  diagnosis.  Ulcerated  constricting  epidermoid  carcinoma 
of  oesophagus  with  extension  to  trachea  and  into  a  cervical  lymph  node. 
Communication  between  trachea  and  oesophagus  through  the  tumor 
extension  into  trachea.  Tuberculosis  of  left  lung  with  cavity  formation 
and  tuberculous  pneumonia.  Tuberculosis  of  mediastinal  lymph  nodes. 
Chronic  and  acute  bronchitis.  Congestion  of  lungs.  Chronic  fibrous 
mitral  endocarditis.  Arterio-sclerosis.  Chronic  fibrous  perihepatitis. 
Passive  congestion  of  liver.  Chronic  interstitial  pancreatitis.  Slight 
chronic  nephropathy.  Double  renal  pelvis  on  right  side.  Focal  hydro- 
nephrosis  on  right  side  due  to  impacted  calculus  in  lower  renal  pelvis. 
Accessory  adrenal  gland. 

Clinical  history.  Male,  white,  age  fifty-two.  Admitted  to  hospital 
three  months  before  death,  complaining  of  emaciation,  loss  of  strength 
and  difficulty  of  swallowing.  Became  progressively  worse,  developed  a 
moderate  temperature  elevation  more  marked  in  the  evening.  Cough 
and  expectoration  profuse.  No  tubercle  bacilli  in  sputum.  A  stricture 
of  the  oesophagus  was  located  at  a  point  23  cm.  from  the  line  of  the  teeth 
and  an  ulcerated  area  demonstrated  by  the  oesophagoscope. 

Body  of  medium  size,  greatly  emaciated,  weight  eighty-five  pounds. 
Teeth  carious.  Moderate  rigor  mortis.  Abdomen  scaphoid.  Slight 
oedema  of  ankles.  Subcutaneous  fat  very  slight  in  amount.  Muscles 
pale. 

Abdominal  cavity  dry.  Slight  adhesions  in  ileocaecal  region.  The 
appendix  densely  adherent  to  ascending  colon.  Marked  ptosis  of  trans- 
verse colon,  this  lying  6  cm.  below  the  umbilicus. 

Spleen,  weight  100  grams,  adherent  to  diaphragm  at  upper  pole. 
Capsule  wrinkled  and  slightly  thickened. 

Adrenal  glands  normal,  i  cm.  anterior  to  left  adrenal  is  a  small  flat 
accessory  gland  i  cm.  in  diameter. 

Left  kidney,  weight,  150  grams.  Capsule  slightly  adherent.  On 
section  consistency  increased.  Cortex  5  mm.  in  thickness,  markings 
obscure.  Pyramids  distinct.  Slight  increase  in  pelvic  fat.  Right 
kidney,  weight,  no  grams.  Densely  adherent  to  surrounding  tissue. 
Lower  pole  distinctly  shrunken  and  separated  by  a  linear  depression 
from  the  main  part  of  the  organ.  Capsule  adherent.  On  section  there 
is  a  cyst  in  the  lower  pole  3  by  2.5  by  2  cm.,  containing  a  thin,  cloudy, 


TERATOID  TUMORS  173 

reddish-brown  fluid.  On  the  inner  surface  there  are  numerous  saccular 
diverticulae  corresponding  to  the  pelvic  calices  and  at  one  point  a  circular 
depression  containing  a  calculus  i  by  1.5  cm.  in  diameter.  There  is  no 
communication  of  this  cyst  with  the  pelvis  nor  with  the  ureter.  The 
upper  portion  of  this  kidney  shows  the  same  condition  as  the  left  kidney. 

Bladder  normal. 

Liver,  weight,  1250  grams.  There  are  focal  thickenings  of  the  capsule 
over  the  convexity,  stellate  in  shape  with  communication  between  the 
branches.  These  do  not  extend  into  the  liver  substance.  On  section 
the  hepatic  veins  and  centres  of  lobules  are  congested. 

Pancreas,  normal  in  size,  very  firm,  cuts  with  increased  resistance; 
the  cut  surface  shows  very  marked  lobulation. 

Stomach  and  intestinal  tract  normal. 

The  right  lung  adherent  to  pleura  by  stringy  fibrous  adhesions. 
Weight  560  grams,  voluminous,  congested.  Drops  of  pus  can  be  squeezed 
from  the  bronchi.  There  is  moderate  congestion  of  the  bronchi  and  a 
considerable  amount  of  adherent,  viscid,  purulent  mucus.  Left  lung 
adherent  at  apex,  weight  650  grams.  Marked  congestion  of  the  tissue. 
In  the  apex  a  cavity  5  cm.  in  diameter,  the  inner  surface  roughened,  the 
wall  composed  of  dense  fibrous  tissue.  Cavity  contains  a  considerable 
amount  of  thick,  viscid,  yellow  fluid,  smears  from  which  show  tubercle 
bacilli.  In  the  upper  lobe  adjoining  the  cavity  there  is  a  yellow  gray 
solidified  area  which  in  places  has  a  gelatinous  appearance.  A  similar 
area  is  in  the  adjoining  upper  portion  of  the  lower  lobe.  In  the  middle 
of  the  lower  lobe  posteriorly  a  pea-sized  encapsulated  mass  of  caseous 
material.  Tissue  elsewhere  is  the  same  as  that  of  right  lung.  Lymph 
nodes  at  the  bifurcation  of  trachea  are  enlarged,  the  mass  composed  of 
them  measuring  5  by  4  cm.  On  section  these  are  pigmented  and  contain 
grayish  white  caseous  nodules. 

Pericardium  normal. 

Heart,  weight,  280  grams.  Left  ventricle  firmly  contracted,  wall 
15  mm.  thick.  Left  auriculo-ventricular  ring,  8.5  cm.  in  circumference, 
shows  thickening  of  the  ring,  retraction  of  valve  leaflets  and  thickening 
along  line  of  closure.  Chordae  tendineae  are  thickened  and  shortened 
and  the  apices  of  papillary  muscles  are  fibroid.  The  aortic  orifice 
measures  8  cm.,  the  valves  slightly  thickened. 

The  aorta  shows  throughout  its  length  plaque-like  yellow  thickenings 
of  intima. 

Mucous  membrane  of  mouth,  pharynx  and  larynx  normal. 

(Esophagus  shows  extensive  ulceration  beginning  at  a  point  2  cm. 
below  the  arytenoid  notch  and  extending  for  a  distance  of  9  cm.  The 
ulcer  for  the  greater  part  involves  the  entire  wall.  At  the  edge  of  the 


174  PATHOLOGY 

ulcer  the  mucous  membrane  is  thickened  and  elevated.  In  the  centre  of 
the  ulcerated  area  there  is  a  slight  saccular  dilatation  and  in  the  lower 
part  an  evident  constriction  of  the  lumen.  The  oesophagus  is  firmly 
adherent  to  the  surrounding  structures,  particularly  to  the  trachea  and 
upper  part  of  the  arch  of  the  aorta  and  the  larger  vessels  of  the  neck.  On 
the  left  side  one  of  the  lower  cervical  lymph  nodes  is  adherent  to  the 
tumor  which  has  extended  into  this. 

Trachea.  At  a  point  3  cm.  below  the  cricoid  there  is  a  greyish  yellow 
elevation  of  the  posterior  surface,  the  size  of  a  split  pea.  By  probing, 
a  minute  communication  between  the  trachea  and  the  oesophagus  is 
found  at  this  point;  1.5  cm.  lower  down  is  a  similar  elevation  but  no 
communication  with  the  oesophagus.  Elsewhere  the  mucous  membrane 
of  the  trachea  is  normal  and  a  considerable  amount  of  tenacious  purulent 
mucus  adheres  to  it. 

REMARKS.  The  main  points  of  interest  in  this  autopsy  are: 
First,  the  carcinoma  of  the  oesophagus  with  its  extensions  into 
trachea  and  into  one  of  the  lower  cervical  lymph  nodes.  It  is 
rather  unusual  that  there  were  not  found  more  metastases,  par- 
ticularly into  the  lungs  and  liver.  The  bronchitis  is  probably  to  be 
attributed  to  infection  of  the  lung  by  means  of  the  communication 
between  the  trachea  and  oesophagus.  The  great  emaciation  of  the 
individual  is  due  to  malnutrition  brought  about  by  the  constriction 
of  the  oesophagus.  Such  physical  interferences  with  nutrition  are 
the  most  prominent  causes  of  the  cachexias  of  the  malignant 
tumors.  Second,  the  tuberculosis  confined  to  one  lung  producing 
cavity  formation  and  tuberculous  pneumonia  with  extension  into 
the  mass  of  lymph  nodes  at  bifurcation  of  the  trachea.  In  this 
connection  also  the  absence  of  tubercle  bacilli  from  the  sputum  is 
interesting.  There  was  a  profuse  discharge  from  the  bronchi,  due  to 
the  bronchitis  and  the  examination  may  have  been  of  material 
from  this  source  and  not  from  the  tuberculous  cavity.  Third, 
the  congenital  malformation  of  the  kidney  shown  in  the  double 
pelvis.  The  hydronephrosis  is  confined  to  the  region  of  one  pelvis 
and  is  due  to  the  blocking  of  the  outlet  by  the  calculus.  Fourth, 
the  chronic  endocarditis  of  the  mitral  valve  with  some  resulting 
contraction  of  the  valve.  This  condition  was  not  sufficient,  how- 
ever, to  have  seriously  interfered  with  the  work  of  the  heart. 


TERATOID  TUMORS  175 

A  CASE  OF  CARCINOMA  or  BREAST 

The  specimen  consists  of  breast  with  a  large  amount  of  muscle  beneath, 
and,  extending  from  this,  tissue  to  which  numerous  lymph  nodes  are 
attached.  The  nipple  is  retracted.  Four  cubic  centimeters  from  the 
nipple  is  an  elevated  nodule,  firmly  attached  to  the  skin.  On  section 
this  is  oval  in  outline  i  by  0.6  cm.  in  diameter,  firm,  of  pearly  gray  color, 
with  opaque  points.  It  is  firmly  attached  on  all  sides  and  passes  without 
demarkation  into  the  corium.  Section  of  the  breast  through  the  de- 
pressed nipple  shows  a  tumor  mass  taking  the  place  of  the  mammary 
gland.  The  tumor  is  dense  and  hard,  cutting  like  cartilage,  of  a  general 
pearly  gray  color,  with  small,  whiter  and  more  opaque  points.  The  mass 
of  tumor  tissue  is  oblong,  the  long  axis  parallel  with  the  surface,  measur- 
ing 6  by  3  cm.  in  greatest  diameter.  The  tumor  cannot  be  separated 
from  the  adjoining  tissue,  the  edge  is  irregular  and  processes  from  the 
tumor  extend  into  the  surrounding  tissue  and  upwards  toward  the 
nipple  which  is  firmly  adherent  to  the  tumor.  The  tumor  also  adheres 
to  the  underlying  pectoral  muscle.  In  the  fat  tissue  of  the  mamma 
2  cm.  from  the  tumor  is  a  firmly  adherent  small  gray  tumor  i  cm.  in 
diameter.  On  scraping  the  cut  surface  with  a  knife  a  small  amount  of 
opaque  thin  fluid  is  obtained.  This,  on  microscopical  examination, 
shows  numerous  epithelial  cells  of  various  size  and  shape,  single  and  in 
groups  and  containing  numerous  fat  drops.  The  adherent  mass  of 
axillary  nodes  shows  one  of  these  converted  into  a  hard  gray  tissue  and 
two  of  the  others,  on  section,  show  small  circumscribed  areas  of  the  same 
tissue. 

The  frozen  sections  of  the  tumor  and  the  axillary  nodes  show  in  the 
breast  a  carcinoma  of  the  medullary  and  scirrhus  type  and  metastatic 
tumors  of  the  same  character  in  the  lymph  nodes. 

REMARKS.  This  is  a  case  of  advanced  carcinoma  of  the  breast 
with  secondary  nodules  in  the  surrounding  tissue  and  with  metas- 
tases  in  the  lymph  nodes.  In  a  case  so  advanced  as  this  complete 
removal  of  all  the  tumor  cells  can  hardly  be  expected  even  in  so 
thorough  an  operation  as  was  done. 

A  CASE  OF  DEATH  FROM  CARCINOMA  OF  BREAST  WITHOUT 
OPERATION 

Anatomical  diagnosis.  Carcinoma  (en  cuirasse)  of  both  breasts  with 
infiltration  of  anterior  thoracic  wall.  Extensive  ulceration.  Extensive 
pleural  metastases.  Metastases  and  extensive  infiltration  of  axillae. 
Single  metastases  in  cerebral  cortex  and  in  lung.  Chronic  adhesive 


1 76  PATHOLOGY 

pleuritis.    Old  tuberculosis  of  apices  of  lungs.    (Edema  of  lungs.    My- 
oma of  uterus. 

Body  that  of  a  white  female,  fifty-seven  years  old,  of  good  physique 
and  good  nutrition.  There  is  a  very  extensive  ulceration  involving 
the  greater  portion  of  the  right  upper  breast  and  extending  up  over  the 
shoulder  and  upper  fifth  of  the  anterior  surface  of  the  right  arm.  The 
ulcerated  surface  is  rough  and  covered  with  much  necrotic,  foul-smelling 
tissue.  The  edges  are  indurated  and  beyond  these  the  skin  shows  numer- 
ous pale-blue  elevations  varying  in  size  from  2  to  8  mm.  The  overlying 
skin  is  adherent  to  these  nodules.  Similar  nodules  also  extend  widely 
beyond  the  edge  of  the  ulcer,  that  is,  from  the  right  shoulder,  anterior 
portion  of  right  arm,  right  axilla,  across  median  line  covering  left 
breast,  portion  of  left  shoulder  and  upper  arm  into  left  axilla,  and  beyond 
this  reaching  to  anterior  border  of  left  scapula.  The  left  nipple  is  absent 
and  in  its  place  is  an  ulcer  7  cm.  in  diameter,  smaller,  but  of  the  same 
character  as  that  on  the  right  side.  Section  through  the  left  breast 
shows  an  extensive  infiltration  with  a  firm  pink  gray  tissue  infiltrating 
fat,  pectoral  muscles  and  in  places  extending  into  the  intercostal  muscles. 
There  is  very  marked  oedema  of  both  upper  extremities  and  shoulders. 
No  oedema  in  lower  extremities. 

Abdominal  fat  3  cm.  in  thickness.  In  peritoneal  cavity  no  excess  of 
fluid,  surface  smooth  with  the  exception  of  slight  adhesions  around  the 
gall  bladder. 

The  anterior  wall  of  thorax  shows  extensive  infiltration  of  all  the  tissue 
with  the  tumor  masses.  The  right  axilla  is  filled  with  a  large  mass  of 
tumor,  the  axillary  vein  thrombosed,  the  nerve  plexus  embedded  in  the 
tumor  mass,  which,  to  some  extent,  extends  along  the  nerve  trunks.  In 
the  left  axilla  the  vein  is  surrounded  by  tumor,  but  the  nerve  plexus  is 
not  so  extensively  involved. 

Both  j>leural  cavities  show  an  increased  amount  of  fluid.  There  are 
a  few  adhesions  at  the  apices.  Beneath  the  anterior  parietal  pleurae 
there  are  numerous  flattened,  slightly  elevated,  gray  nodules  from  2  to 
6  mm.  hi  diameter. 

Pericardial  cavity  normal.  Heart  weighs  250  grams.  Myocardium 
and  valves  normal.  Lungs  show  cicatricial  thickening  at  both  apices 
corresponding  with  pleural  adhesions.  Lower  posterior  portions  are 
congested  and  contain  much  fluid.  In  the  right  lung  posteriorly  im- 
mediately beneath  pleura  there  is  a  small  gray  nodule  8  mm.  in  diameter. 

Mucous  membrane  of  mouth  rather  pale.  Pharynx,  larynx,  trachea 
and  oesophagus  normal. 

Liver,  spleen,  pancreas  and  kidneys  show  no  change  other  than  slight 
post-mortem  discoloration.  In  aorta  a  few  slightly  elevated,  small, 


TERATOED  TUMORS  177 

yellow  plaques  most  marked  in  abdominal  portion.  The  lymph  nodes 
with  the  exception  of  axillary  show  no  change. 

Stomach  and  intestines  normal. 

Uterus  small,  contains  posteriorly  a  small  intramural  myoma,  3  cm. 
in  diameter. 

Calvarium  and  scalp  normal.  The  dura  is  intensely  adherent  to 
calvarium;  3  cm.  behind  the  fissure  of  Rolando  and  2.5  cm.  from  the 
longitudinal  fissure  on  right  side  is  a  single  grey-white,  slightly  elevated 
tumor  1.5  cm.  in  diameter.  On  section  it  is  sharply  circumscribed. 
The  brain  is  of  uniform,  firm  consistency. 

REMARKS.  Of  interest  is  the  great  local  extension  of  tumor  with 
ulceration.  The  tumor  probably  was  primary  in  right  breast,  the 
left  representing  an  extension.  All  of  the  lymphatic  vessels  in  the 
region  are  involved.  The  direct  extension  of  the  tumor  through 
the  chest  walls  to  the  pleura  is  not  very  unusual.  The  metastasis 
in  the  lung  may  have  been  hsematogenous  in  origin  or  the  visceral 
pleura  may  have  been  invaded  from  without  and  the  tumor  ex- 
tended into  the  lung.  The  cerebral  tumor  represents  a  metastasis 
by  the  blood  stream.  It  also  is  rather  striking  that  the  metastases 
are  not  more  numerous.  The  cedema  of  both  upper  extremities 
is  due  to  compression  of  axillary  veins  by  the  tumor  mass  about 
them.  On  the  right  side  this  was  accentuated  by  the  thrombus. 
Of  interest  also  is  the  general  good  nutrition,  the  absence  of  cachec- 
tic condition.  In  such  cases  we  should  expect  to  find  extensive 
amyloid  infiltration.  We  must  assume  that  in  cases  such  as  this 
the  body  establishes  an  immunity  against  the  toxic  substances 
which  must  have  been  absorbed  from  the  extensive  sloughing 
ulcers. 

CLINICAL  HISTORY.  The  patient,  a  female,  age  38,  entered  Hunting- 
ton  Memorial  Hospital  April  27th,  1912.  She  stated  that  a  lump  ap- 
peared in  left  side  of  abdomen  seven  years  previously.  This  grew 
slowly  and  a  year  ago  it  began  to  cause  pain.  She  entered  the  Massa- 
chusetts General  Hospital,  June  19,  1911,  and  the  following  day  an 
operation  was  performed  consisting  in  a  median  incision  5  inches  long 
into  the  abdomen  above  the  umbilicus.  On  palpating  the  stomach 
after  the  incision  a  firm,  hard  tumor  as  broad  as  the  palm  of  the  hand 
was  found  which  involved  the  posterior  wall  of  the  stomach.  The 
growth  had  extended  through  the  posterior  wall  and  could  be  seen  on 
lifting  the  stomach  as  a  small  nodular  excresence  about  i  cm.  in  diam- 


178  PATHOLOGY 

eter.  The  diagnosis  of  carcinoma  was  made  and  gastro-enterostomy 
performed,  a  loop  of  jejunum  being  united  to  anterior  wall  of  stomach. 
Patient  remained  four  weeks  in  the  hospital. 

The  lump  in  the  abdomen  continued  to  grow  slowly  and  became 
painful  especially  after  exercise.  On  February  last  she  had  an  un- 
usually severe  attack  of  pain  in  left  side  of  abdomen  which  extended  to 
left  leg.  Since  her  operation  she  has  been  able  to  take  liquids  and  soft 
foods  only  and  has  been  much  troubled  by  indigestion.  The  remote  and 
family  history  of  patient  are  negative. 

On  admission  into  Huntington  Memorial  Hospital  patient  appears  as 
a  well-built  but  rather  emaciated  female.  Skin  and  mucous  membranes 
pale.  Lungs  negative.  Heart  —  the  cardiac  area  normal.  At  the  apex 
a  short  blowing  murmur  is  heard  accompanying  the  first  sound.  The 
abdomen  is  soft  and  depressed.  Pulsation  of  abdominal  aorta  can  be 
seen  and  palpated.  In  the  median  line  between  ensiform  cartilage  and 
umbilicus  is  a  linear  cicatrix,  at  the  central  point  of  which  is  a  small, 
red  elevated  nodular  area  resembling  granulation  tissue.  Beneath  the 
upper  end  of  the  cicatrix  an  irregular  hard  area,  approximately  4  by  3  cm., 
can  be  felt.  There  are  numerous  ill-defined  masses  to  be  felt  in  the 
gastric  region.  The  epigastric  region  is  somewhat  full  on  percussion 
and  resistant  to  the  touch.  The  hepatic  dullness  extends  from  the 
seventh  rib  to  two  finger  breadths  below  the  costal  margin.  At  the 
costal  margin  along  the  inner  axillary  line  a  rounded,  firm  mass,  approxi- 
mately 4  cm.  in  diameter,  can  be  felt.  Splenic  dullness  is  not  enlarged. 
Kidneys  are  palpable. 

During  the  patient's  residence  in  hospital  the  nodule  in  the  cicatrix 
rapidly  increased  in  size  and  the  palpable  masses  beneath  the  upper 
margin  of  the  abdominal  cicatrix  appeared  to  enlarge.  She  complained 
of  burning  and  gnawing  sensations  in  the  stomach.  There  was,  at  times, 
very  considerable  abdominal  distension,  chiefly  after  eating.  On 
June  24  patient  vomited  large  blood  clots  and  bloody  fluid,  and  June  25th 
had  a  large  bloody  stool.  The  abdominal  pain  increased  and  note  on 
July  iQth  states  that  "the  attacks  are  frequent,  very  severe  and  come 
on  without  warning.  During  an  attack  the  abdomen  becomes  rigid 
and  the  intestines  can  be  felt  to  contract  strongly  and  then  relax."  At 
this  time  there  was  noted  a  number  of  minute  subcutaneous  nodules 
over  the  abdomen.  The  pain  and  emaciation  continued  and  slight 
oedema  of  the  hands  and  feet  developed.  Patient  died  July  3oth,  hav- 
ing been  practically  moribund  for  five  days  before  death. 

Blood  examination  during  her  stay  in  the  hospital  showed  a  pro- 
gressive diminution  in  blood  cells  and  haemoglobin.  The  last  count  on 
July  1 5th  showed  red  cells  2,520,000  and  haemoglobin  reduced  to  35 


TERATOID  TUMORS  179 

per  cent.  During  her  entire  stay  in  the  hospital  there  was  a  slight  and 
irregular  elevation  of  temperature,  practically  not  extending  beyond 
38.7°  C.  On  July  24th  began  a  considerable  rise,  extending  on  the 
27th  to  39.7  with  a  gradual  fall  to  37.8  before  death,  which  occurred 
July  29th. 

Anatomical  diagnosis.  Carcinoma  of  stomach  with  metastases  to 
liver,  adjacent  lymph  glands,  omentum,  pancreas,  adrenals,  perito- 
neum, small  intestine,  ovary,  abdominal  wall,  ribs  and  sternum;  Occlu- 
sion of  pylorus;  Gastro-enterostomy;  Chronic  fibrous  pleuritis;  sec- 
ondary anaemia;  Hyperplasia  of  bone  marrow;  Fatty  degeneration. 

Autopsy.  The  body  is  that  of  a  well-developed  and  greatly  ema- 
ciated white  woman.  There  is  a  moderate  degree  of  rigor  mortis.  The 
abdominal  wall  is  retracted  and  presents  in  the  region  of  the  epigastrium 
a  mass  covered  with  skin  measuring  6  by  5  by  5.5  cm.  elevated  4  cm. 
above  the  surface.  From  the  lower  border  of  this  mass  there  is  a  smooth, 
linear  scar  extending  3  cm.  in  the  direction  of  the  umbilicus.  There  is 
also  an  indurated  and  slightly  elevated  area  5  cm.  across,  which  ex- 
tends from  the  costal  margin  toward  the  umbilicus.  On  the  inner  as- 
pect of  the  right  leg  there  are  a  number  of  tortuous  firm  veins.  Sub- 
cutaneous fat  very  small  in  amount,  muscles  pale. 

PL^URAL  CAVITIES.  Contain  no  fluid;  the  surface  of  the  superior 
lobe  of  the  right  lung  is  adherent  everywhere  to  the  wall  of  the  thorax, 
but  adhesions  are  readily  broken. 

PERITONEAL  CAVITY.  Contains  400  c.c.  of  yellowish,  watery  fluid. 
The  mass  presenting  externally  in  the  epigastrium  is  found  to  involve 
not  only  the  abdominal  wall,  but  the  round  ligament  of  liver.  On 
section  the  interior  of  this  mass  is  somewhat  softened,  and  on  pressure  a 
soft,  puriform  material  exudes.  The  edges  of  the  liver  extend  beyond 
the  umbilicus  and  numerous  tumor  nodules  are  seen  in  it.  The  right 
ovary  contains  numerous  cysts  and  is  infiltrated  with  tumor  tissue.  A 
loop  of  the  jejunum  is  adherent  to  the  lower  portion  of  the  anterior  wall 
of  the  stomach  and  the  transverse  colon  runs  posteriorly  to  this.  There 
is  a  flattened  nodule  in  the  omentum,  measuring  1.5  cm.,  and  several 
smaller  nodules. 

PERICARDIAL  CAVITY.    Contains  a  small  amount  of  fluid. 

HEART.  Weight  172  grams.  On  its  anterior  surface  is  a  nodule 
0.8  cm.  in  diameter,  of  firm  consistency  and  pale  pink  color.  In  other 
parts  of  the  myocardium  are  several  other  small  modules  of  similar 
character.  The  heart  valves  are  normal. 

LUNGS.    Negative. 

INTESTINES.  Beneath  the  mucosa  of  the  small  intestine  is  a  minute 
nodule  3  mm.  in  diameter.  The  intestinal  canal  is  otherwise  normal. 


i8o  PATHOLOGY 

SPLEEN.  Weight  183  grams.  Somewhat  pale  and  softer  than 
normal. 

PANCREAS.  Is  small;  attached  to  the  tail  is  a  tumor  nodule,  measur- 
ing 1.8  cm.  in  diameter,  of  the  same  character  as  the  tumors  else- 
where. 

LIVER.  Weight  3131  grams.  The  large  organ  is  infiltrated  with 
tumor  tissue.  The  tumor  masses  vary  in  size  from  ^  cm.  to  12  cm.  in 
diameter.  The  larger  nodules  are  definitely  umbilicated  with  deep  de- 
pression in  the  centre  and  elevated  edges.  On  section  the  tumor  tissue 
is  a  pale  gray  color  with  pink  tinge.  The  interior  of  the  large  masses  is 
necrotic.  The  liver  substance  is  pale.  The  markings  are  indistinct. 
The  liver  is  adherent  to  the  stomach  and  transverse  colon.  The  gall 
bladder  and  ducts  are  normal. 

STOMACH.  The  pyloric  portion  of  the  stomach  is  involved  in  a  tumor 
growth  which  extends  7  cm.  from  the  pylorus  and  appears  as  an  irregular 
mass  involving  the  wall.  The  central  part  of  the  mass  is  softened  and 
the  edges  are  irregularly  elevated.  The  opening  between  stomach  and 
jejunum  is  nodular  at  the  edges.  The  pylorus  is  closed. 

ADRENALS.  The  right  adrenal  contains  a  small  tumor  nodule  0.4  cm. 
in  diameter,  and  in  the  left  adrenal  is  a  larger  nodule  1.5  cm.  in  dia- 
meter. 

KIDNEYS.  Combined  weight  of  kidneys,  257  grams.  Between  the 
peritoneum  and  the  surface  of  the  left  kidney  are  a  number  of  small, 
flat  nodules  the  edges  measuring  7  mm.  The  kidneys  are  pale  but  other- 
wise normal.  The  ureters  are  of  normal  calibre  and  patent  throughout. 

Bladder  and  uterus  unimportant. 

OVARY.  The  right  ovary  is  replaced  by  a  nodular  mass  of  tumor 
tissue  -measuring  7  by  9  by  4  cm.  Within  this  are  numerous  cysts  filled 
with  clear,  yellow  fluid. 

AORTA.    Normal. 

Retro-peritoneal  lymph  nodes  are  enlarged,  pale  pink  in  color. 

BONE  MARROW.  In  lower  end  of  femur  the  marrow  is  of  a  yellowish, 
translucent  color.  In  the  upper  portion  soft  and  red. 

BONES.  On  the  inner  aspect  of  the  sternum  is  a  flat  protuberance 
4  cm.  in  length.  The  bone  over  the  area  is  soft  and  crepitant  and  the 
interior  is  filled  with  reddish,  soft  tissue.  There  is  a  similar  area  in  the 
lower  portion  of  the  sternum.  The  third  rib  on  the  right  side  presents 
a  fusiform  swelling  extending  10  cm.  from  the  sternal  end.  The  swell- 
ing is  4  by  3  cm.  in  diameter  and  consists  of  a  soft  shell  of  bone  which 
crepitates  on  pressure.  The  interior  is  filled  with  reddish,  pulpy  tissue. 
On  the  eighth  rib  is  a  thickened  area,  4  cm.  in  length,  of  the  same  char- 
acter as  that  in  the  third  rib. 


TERATOID  TUMORS  181 

BRAIN.  Weight  1205  grams.  Convolutions  are  prominent,  the  sulci 
wide  and  deep,  the  general  appearance  resembling  that  of  an  atrophied 
brain  of  old  age.  The  ventricles  are  negative. 

MICROSCOPICAL  EXAMINATION.  The  exudation  in  abdominal  cavity 
contains  a  considerable  number  of  large,  rather  pale  cells  of  epithelial 
character,  which  are  single  or  attached  forming  small  groups.  Sections 
of  the  stomach  show  the  tumor  to  be  a  carcinoma  which  has  infiltrated 
the  entire  wall.  Section  of  the  rib  shows  on  the  surface  fibrous  tissue 
enclosing  alveoli  of  the  tumor.  The  bone  trabeculae  are  small  and  in 
places  necrotic.  About  the  necrotic  bone  there  is  a  considerable  forma- 
tion of  osteoid  tissue  with  masses  of  tumor  cells  between  the  trabeculae. 
The  process  represents  an  extensive  necrosis  and  destruction  of  bone 
with  very  imperfect  renewal.  Sections  of  the  liver  show  great  atrophy 
of  the  liver  tissue,  the  tumor  mass  having  the  usual  characteristics. 
Section  of  the  tumor  in  epigastric  region  shows  extensive  tissue  necrosia. 
The  heart  and  kidney  stained  for  fat  show  marked  fatty  degeneration. 
This  is  general  and  diffuse  in  the  heart.  In  the  kidney  the  degeneration 
is  confined  to  the  collecting  tubules  and  ascending  arm  of  the  Henle 
loops. 

REMARKS.  There  are  many  points  of  interest  in  the  case.  The 
age  of  the  patient  is  rather  below  the  age  at  which  carcinoma  of 
the  stomach  is  most  frequent.  The  statement  of  the  patient  as  to 
the  presence  for  seven  years  of  a  lump  in  the  abdomen  must  be 
taken  with  a  certain  reserve;  it  is  improbable  that  the  process 
began  so  long  ago.  The  gastro-enterostomy  was  performed  to  re- 
lieve the  stenosis  of  the  pylorus  which  the  tumor  produced.  The 
disease  at  the  time  of  operation  was  so  advanced  that  radical  re- 
moval could  not  be  undertaken. 

The  emaciation  of  the  patient  is  due  in  part  to  the  interference 
with  the  function  of  the  stomach,  in  part  to  the  constant  pain, 
and  in  part  to  the  toxic  absorption.  The  effect  of  this  on  metabo- 
lism is  shown  by  the  marked  fatty  degeneration  of  the  heart  and 
kidneys  apparent  on  microscopic  examination.  The  anaemia,  an- 
other marked  feature,  is  due  to  the  malnutrition,  to  the  haemolytic 
action  of  toxic  absorption,  and  to  haemorrhage  from  the  tumor, 
which  is  shown  by  the  vomiting  of  blood  and  the  bloody  stools. 
The  red  bone  marrow  of  the  femur  is  evidence  of  blood  regenera- 
tion following  the  anaemia  to  which  the  cardiac  murmur  is  also 
due. 


182  PATHOLOGY 

The  slight  and  constant  elevation  of  temperature  during  her  stay 
in  the  hospital  is  evidence  of  the  effect  of  absorption  of  toxic 
products.  The  small  size  of  the  heart  shows  that  this  organ  shares 
in  the  general  atrophy  of  the  body.  The  tumor  in  the  stomach 
has  the  general  character  of  carcinoma  of  the  alimentary  canal, 
necrosis  and  ulceration  in  the  centre  with  wall-like  peripheral 
growth.  The  area  involved  is  large,  the  pylorus  completely 
dosed  and  the  opening  into  the  jejunum  also  encroached  upon. 
The  situation  of  the  prominent  subcutaneous  tumor  in  the  epi- 
gastrium in  the  line  of  the  scar  is  probably  due  to  the  inclusion  of 
tumor  cells  in  the  wound  at  the  time  of  the  operation.  The  growth 
of  this  during  the  last  two  months  was  very  rapid.  The  growth  of 
the  large  masses  in  the  liver  and  in  the  primary  tumor  may  have 
been  equally  rapid,  but  was  marked  by  the  central  necrosis  and 
absorption.  The  rapid  growth  and  absorption  are  shown  by  the 
deep  central  depression  in  the  liver  metastases.  The  metastases 
are  due  chiefly  to  conveyance  of  the  tumor  cells  by  the  blood 
stream.  They  are  most  numerous  in  the  liver,  as  is  to  be  ex- 
pected. The  bone  metastases  are  more  extensive  than  usual.  These 
develop  in  the  medullary  cavity  and  as  the  tumor  enlarges  there  is 
constant  destruction  and  new  formation  of  the  surrounding  bone. 
The  old  bone  does  not  expand.  In  the  present  case  there  was  a 
thin  shell  of  bone  over  the  tumor,  which  was  partly  necrotic  and 
partly  imperfectly  calcined  new  bone;  the  rubbing  of  the  spicules 
on  pressure  produced  the  crepitation.  The  tumor  cells  also  passed 
into  the  peritoneal  cavity  as  is  shown  by  their  presence  in  the  exu- 
dation. The  large  tumor  of  the  ovary  is  to  be  attributed  rather  to 
extension  into  this  of  a  peritoneal  implantation  than  to  metastasis 
by  the  blood.  The  involvement  of  the  lymph  nodes  is  less  marked 
than  is  usual. 

A  CASE  OF  MELANOTIC  SARCOMA 

Female,  white,  age  thirty-two.  A  pigmented  mole,  size  of  nail  of  index 
finger,  on  back  of  neck  in  median  line  over  spine  of  vertebra  prominens. 
Eight  months  before  induration  was  noticed  about  and  beneath  the 
mole.  Since  then  growth  has  been  progressive,  at  first  slowly,  lately 
more  rapidly. 

Received  for  examination  an  area  of  skin  and  subcutaneous  tissue 
which  contained  a  small  tumor  2.5  cm.  in  diameter.  This  tumor  is 


TERATOID  TUMORS  183 

firmly  adherent  to  the  overlying  skin.  On  section  the  tumor  is  of  firm 
homogeneous  consistency,  and  of  a  mottled  brown  to  black  color.  The 
tumor  tissue  passes  into  the  epidermis  over  it. 

Microscopically  it  consists  of  masses  of  cells  with  small  strands  of 
dense  connective  tissue  between  them.  The  connective  tissue  is  small 
in  amount,  contains  but  few  cells  and  seems  to  represent  only  the  dense 
tissue  of  the  corium  separated  by  the  cells.  There  are  numerous  large, 
thin-walled  vessels  in  the  connective  tissue.  In  the  seemingly  separated 
cell  masses  single  connective  tissue  fibrils  and  capillary  vessels  can  be 
seen  along  which  the  tumor  cells  often  are  arranged  as  palisades.  The 
cells  are  of  much  the  same  size,  their  shape  influenced  by  mutual  pressure. 
Most  of  them  are  free  from  pigment,  others  contain  brown  or  black  pig- 
ment in  granular  form.  At  the  periphery  the  tumor  cells  infiltrate  the 
tissue.  There  are  numerous  nuclear  figures  in  the  cells. 

Diagnosis,  melanotic  sarcoma.    Prognosis  unfavorable. 

A  CASE  OF  SARCOMA  or  PENIS 

The  following  case  is  a  sarcoma,  unusual  in  situation  and  of  malig- 
nant character.  There  are  three  laboratory  records  of  the  tumor.  The 
first  says:  A  small  piece  of  tissue  removed  from  a  growth  on  the 
penis.  Examination  shows  masses  of  spindle  and  irregular  cells  rather 
loosely  arranged.  In  the  masses  are  large  vascular  spaces.  Diagnosis, 
sarcoma. 

The  next  examination  is  of  the  amputated  end  of  the  penis.  This 
showed  a  small  tumor  3.5  by  1.5  cm.  projecting  into  the  urethra  and 
attached  to  the  lower  surface  of  this  over  an  area  1.5  by  i  cm.  On 
section  gray,  of  homogeneous  consistency  with  a  few  irregular  fissures. 
The  tip  of  the  tumor  projects  through  the  meatus  and  is  necrotic.  The 
urethra  posterior  to  the  tumor  is  dilated.  Microscopical  section  through 
the  tumor  and  adjoining  urethra  shows  a  covering  of  intact  mucous 
membrane  which  is  thickened  where  the  tumor  projects  from  it  and 
infiltrated  with  lymphoid  cells.  At  the  base  of  the  tumor  there  is  marked 
infiltration  with  lymphoid  cells.  The  tumor  is  composed  of  masses  of 
spindle  and  irregular  cells  which  contain  numerous  nuclear  figures. 
There  are  numerous  fissures  lined  with  endothelium  and  many  of  these 
contain  red  blood  corpuscles. 

The  third  note  is  after  four  months.  The  entire  penis  and  one  in- 
guinal lymph  node  were  removed.  At  distal  end  of  the  penis  is  an  ele- 
vated cauliflower  growth  extending  backwards  2  cm.  without  sharp 
limitation.  The  lymph  node  removed  is  egg-shaped,  smooth,  3  by  4  era. 
in  diameter. 


1 84  PATHOLOGY 

Microscopically,  the  growth  in  the  penis  and  lymph  node  shows  the 
same  general  character  of  the  tumor  previously  removed,  but  the  cells 
in  most  places  have  a  definite  concentric  mantel-like  arrangement  about 
the  blood  vessels.  The  vessels  with  the  connected  cell  mantels  can  be 
pulled  as  strands  from  the  affected  lymph  node.  Prognosis  unfavorable, 
further  history  unknown. 

A  CASE  OF  LYMPHOMA 

Anatomical  diagnoses.  Lymphoma.  Primary  in  lymph  node.  Meta- 
stases  in  liver,  spleen,  kidneys,  adrenals,  intestinal  canal,  lung,  bone 
marrow  and  epicardium.  Multiple  haemorrhages  in  skin,  mucous  mem- 
branes and  epicardium.  Enlargement  of  liver  and  spleen.  Emphys- 
ema. Arterio-sclerosis.  Cicatrix  of  lung. 

White,  female,  age  fifty-six  years.  Entered  hospital  April  twenty,  1907. 
Loss  of  appetite  and  strength  for  last  two  years.  Eight  weeks  before 
entrance  lymph  nodes  of  neck  became  enlarged.  Two  weeks  later  joints 
were  swollen  and  painful.  Subsided  under  treatment.  At  entrance  pur- 
puric  spots  present  on  legs.  Dyspnea  and  a  sore  throat  developed  April 
twenty-one.  Sputum  very  profuse,  contained  much  blood.  Increase  of 
dyspnea  up  to  tune  of  death,  April  twenty-seven.  Deafness  appeared  April 
twenty-one  and  became  very  much  worse.  On  examination,  pupils  small 
and  sluggish;  exceedingly  deaf.  Enlarged  lymph  nodes  in  neck,  axillae 
and  groin.  Sonorous  and  sibilant  rales  in  lung.  Heart  sounds  weak. 
Liver  enlarged.  Area  of  dullness  in  left  side  suggesting  enlarged  spleen 
pushed  down  by  liver.  Dullness  extended  to  two  fingers  breadths  above 
the  crest  of  the  ileum.  Liver  and  spleen  tender.  Over  lower  abdomen, 
labia  and  inner  and  outer  portions  of  thigh  scattered,  minute,  bright  red 
ecchymoses.  Elsewhere  over  body  larger  and  darker  ecchymoses. 
Blood  count  showed  16000  leucocytes,  40  per  cent  of  lymphocytes. 

Autopsy  twelve  hours  after  death. 

Body  is  that  of  a  middle  age  woman  of  large  frame.  Rigor  mortis 
present.  Subcutaneous  fat  abundant.  Face,  ears  and  hands  cyanotic. 
Abdomen  slightly  distended.  There  are  petechiae  over  the  arms  and 
ankles  most  abundant  about  pubis  and  inner  sides  of  thighs.  Slight 
oedema  of  ankles.  The  cervical  nodes  on  both  sides  are  swollen  and 
about  the  size  of  a  pigeon's  egg.  One  node  palpable  in  right  axilla, 
one  in  left.  Inguinal  nodes  enlarged  to  about  the  size  of  an  English 
walnut,  soft,  discrete  and  movable.  On  opening  abdomen  liver  is 
enlarged  reaching  to  5  cm.  above  the  umbilicus  in  the  middle  line. 
Spleen  also  enlarged.  The  intestines  are  injected,  their  walls  thickened. 

Peritoneal  cavity  contains  small  amount  of  .clear  fluid.  Surface  smooth 
and  glistening.  Lymph  nodes  along  the  lesser  curvature  of  the  stomach, 


TERATOID  TUMORS  185 

the  peri-portal,  the  mesenteric  and  retroperitoneal  are  enlarged,  those 
about  the  head  of  the  pancreas  being  the  most  affected.  The  largest  of 
these  nodes  measures  0.5  by  5  cm. 

Thoracic  cavity  is  free  with  the  exception  of  a  few  slight  adhesions. 
Pleural  surfaces  smooth.  Lungs  voluminous,  everywhere  crepitant 
except  for  a  few  small,  semiconsolidated  areas  at  the  bases  posteriorly. 
There  is  an  irregular  pigmented  cicatrix  at  the  left  apex.  At  the  bifur- 
cation of  the  trachea  is  a  mass  of  enlarged  nodes  varying  in  size  from 
0.5  to  4  cm.  The  vagi  pass  on  either  side  of  this  mass  and  are  not  in- 
volved in  it.  The  nodes  at  hila  of  the  lungs  and  along  the  trachea  also 
are  enlarged.  The  mucous  membrane  of  the  trachea  and  bronchi 
injected,  in  places  haemorrhagic  with  grayish  spots  up  to  2  mm.  beneath 
the  surface. 

Heart.  Weight  290  grams.  Right  side  distended  with  pale  clots 
which  have  a  greenish  tinge  at  edges  and  are  more  opaque  than  usual. 
There  are  ecchymoses  beneath  the  epicardium  of  the  right  auricle.  The 
wall  of  the  right  ventricle  is  9  mm.  thick,  the  left  1.3  cm.  The  edges  of 
mitral  and  tricuspid  valves  are  thickened.  Aorta  throughout  shows 
numerous  slightly  elevated  yellowish  plaques. 

Liver.  Weight  2580  grams.  Surface  shows  a  white  mottling.  On 
section,  white  lines  appear  along  the  course  of  the  portal  vessels. 

Spleen.  Weight  535  grams,  15  by  6  by  9  cm.  Pulp  is  soft,  bright  red 
in  color.  Surface  shows  a  whitish  mottling. 

Pancreas.    Normal. 

Kidneys.  Slightly  enlarged,  combined  weight  330  grams.  Cortex 
of  normal  thickness,  yellowish,  with  indistinct  markings  and  contains 
a  number  of  white  nodules  up  to  3  mm.  in  diameter,  elongated,  the  long 
axis  perpendicular  to  the  surface. 

Adrenals.    Normal. 

Bladder.    Normal. 

Uterus.  Adenexa  normal.  A  few  small  haemorrhages  in  the  vaginal 
mucosa. 

Gastro-intestinal  tract.  The  gastric  mucosa  is  haemorrhagic  and  the 
stomach  wall  contains  numerous  small  nodules  hi  its  substance.  The 
intestinal  mucosa  also  is  haemorrhagic,  the  walls  are  thick,  but  there  is  no 
macroscopic  hyperplasia  of  the  lymphoid  tissue. 

Lymph  nodes.  The  lymph  nodes  everywhere  present  the  same 
appearance.  They  usually  are  discrete  and  encapsulated,  soft,  occasion- 
ally almost  diffluent  on  section.  The  cut  surface  is  smooth,  homo- 
geneous gray  yellow  and  often  mottled  with  haemorrhage.  Marrow  from 
shaft  of  femur,  ribs  and  vertebra  pinkish  red  and  soft. 

Histological  examination.    Lungs.    The  scar  at  the  apex  composed  of 


1 86  PATHOLOGY 

pigmented  cicatricial  tissue  in  which  are  small  cavities  representing 
alveoli  with  thickened  walls.  In  this  area  and  in  the  vicinity  are 
large  numbers  of  round  cells.  In  the  thickened  tissue  there  are  greatly 
dilated  lymphatics  filled  with  cells  of  the  large  lymphoid  type.  The 
alveoli  of  the  lung  are  generally  large,  their  walls  atrophic.  There  are 
numerous  collections  of  lymphoid  cells  about  the  vessels  and  in  the  walls 
of  the  alveoli.  The  capillaries  are  dilated.  In  places  the  alveoli  contain 
red  corpuscles  and  desquamated  epithelial  cells. 

Trachea.  Shows  great  dilatation  of  the  vessels  of  the  mucosa  with 
diffuse  haemorrhage.  All  of  the  vessels  contain  large  cells  of  the  lymphoid 
type  sometimes  among  the  red  corpuscles,  oftener  in  clumps.  In  some 
of  the  vessels  are  collections  of  fibrin  enclosing  in  the  meshes  large  cells. 
In  the  interstitial  tissue  between  the  vessels  there  are  numbers  of  cells 
of  the  same  lymphoid  type  both  in  masses  and  as  a  diffuse  infiltration. 
The  mucous  glands  of  the  trachea  show  a  diffuse  infiltration  with  the 
same  cells,  extending  from  this  and  in  one  place  reaching  up  to  the  sur- 
face are  tumor-like  masses  of  the  same  large  cells. 

Stomach.  Mucosa  and  submucosa  infiltrated  with  small  lympho- 
cytes and  few  larger  mononuclear  and  plasma  cells  with  foci  of  haemor- 
rhage. There  are  collections  of  similar  cells  about  the  vessels. 

Liver.  A  section  stained  with  methylene  blue  and  eosin  shows  to  the 
naked  eye  blue  masses  in  a  more  or  less  well-defined  reticulum  extending 
between  irregular  reddish  areas.  Microscopically,  the  periportal  tissue 
contains  numerous  nodules  in  tumor-like  form  composed  of  masses  of 
cells  diffusely  scattered  hi  a  slight  reticulum.  Similar  though  smaller 
nodules  of  the  same  tissue  are  found  within  the  lobules.  There  is  very 
slight  infiltration  around  some  of  the  hepatic  veins.  The  capillaries  are 
dilated;  they  contain  red  blood  corpuscles,  a  few  polynuclear  cells  and 
numerous  cells  of  the  lymphoid  type.  The  cells  in  the  tumor-like 
masses  are  irregular  in  outline,  the  cytoplasm  small  in  amount  staining 
slightly  with  blue;  no  definite  granulation.  The  nuclei  are  large 
vesicular,  with  numerous  chromatin  granules  and  there  are  numerous 
nuclear  figures.  The  cells  show  little  variation  in  size.  Measurement 
of  twenty  shows  the  average  size  of  8  by  5  /*.  There  is  no  direct  exten- 
sion of  the  cells  of  the  nodules  into  the  sinusoids  of  the  liver. 

Spleen.     Shows  a  diffuse  infiltration  with  large  lymphoid  cells. 

Kidneys.  There  is  a  nodular  infiltration  of  large  cells  at  various 
places  between  the  tubules  of  the  cortex.  There  also  are  nodules  where 
the  tissue  is  almost  completely  substituted  by  the  tumor  cells,  longitudinal 
tubules  being  found  in  these  with  no  destruction  of  epithelium.  Here 
and  there  the  tumor  cells  have  penetrated  the  membrana  propria  and 
are  found  beneath  the  epithelium.  In  the  straight  vessels  of  the  pyra- 


TERATOID  TUMORS  187 

mids  there  are  large  collections  of  lymphoid  cells.  Very  numerous  simi- 
lar cells  are  found  in  the  capillaries  of  the  glomeruli.  In  addition  there 
is  considerable  thickening  of  the  glomerular  vessels  and  an  increase  in 
the  cells  between  them. 

Heart.  The  heart  shows  diffuse,  in  places  nodular  lymphoid  infiltra- 
tion of  the  epicardium  and  considerable  haemorrhage. 

Adrenal  shows  nodular  masses  of  tumor-like  tissue  with  disappearance 
of  the  glandular  tissue  between  them  and  extending  out  from  this  a 
diffuse  infiltration  between  the  tubules.  No  trace  of  gland  tissue  can  be 
seen  where  the  tumor  tissue  is  most  developed. 

Lymph  nodes.  All  these  show  the  same  change.  The  whole  tissue 
of  the  nodes  is  substituted  by  a  diffuse  formation  of  the  large  round  cells. 
In  most  places  there  is  no  evidence  of  capsule  and  the  tumor  growth 
extends  from  the  glands  into  the  surrounding  tissue. 

Bone  marrow.  The  bone  marrow  gives  the  usual  picture  of  an  active 
marrow,  but  there  are,  in  addition,  foci  where  the  marrow  is  entirely 
replaced  by  circumscribed  collections  of  the  same  tumor  cells  as  seen 
elsewhere. 

REMARKS.  A  typical  case  of  lymphoma  with  metastases.  In 
regard  to  the  numbers  of  lymphocytes,  there  is  great  discrepancy 
between  the  clinical  blood  count  and  the  contents  of  the  vessels. 
It  is  possible  that  the  deafness  was  due  to  formation  of  lymphoid 
tissue  in  the  internal  ear. 

A  CASE  OF  MYELOGENOUS  LEUKEMIA 

Anatomical  diagnosis.  Myelogenous  leukemia.  Diffuse  purulent 
infiltration  of  subcutaneous  tissue  of  neck  extending  into  parotid. 
Abscess  of  lung.  Leukemic  enlargement  of  liver  and  spleen.  Haemor- 
rhages and  infarction  of  spleen.  Haemorrhagic  infiltration  of  intestinal 
mucosa.  Primary  tuberculous  ulcer  of  ileum. 

White,  male,  age  twenty-seven  years.  Entered  hospital  complaining 
of  general  weakness  which  has  been  increasing  for  two  years,  and  pain 
and  swelling  below  the  ear. 

On  examination,  ill-nourished  and  pale,  muscles  atrophied.  Mucous 
membranes  pale,  slight  yellowish  tinge  in  conjunctiva.  Abdomen 
greatly  enlarged.  No  evidence  of  ascites.  Abdominal  walls  thin,  liver 
dullness  greatly  increased,  in  erect  posture,  extending  below  umbilicus. 
Corresponding  to  lower  border  of  dullness,  the  large  rounded  edge  of  the 
liver  can  be  felt.  The  area  of  splenic  dullness  merges  above  into  that 
of  liver,  extends  laterally  from  mid-clavicular  to  mid-axillary  line  and 
below  to  the  crest  of  the  ileum.  When  the  patient  stands  there  is  an 


188  PATHOLOGY 

abdominal  protuberance  corresponding  to  this  area.  Heart  action  some- 
what feeble  and  irregular,  no  murmurs.  No  dullness  in  lungs,  a  few 
rales  at  base  on  both  sides.  Has  slight  cough.  On  the  left  side  of  neck 
is  an  indurated,  poorly  denned  swelling,  most  prominent  behind  the 
angle  of  jaw  and  involving  an  area  about  5  cm.  in  diameter.  At  the 
apex  there  are  three  small  ragged  openings  from  which  a  thin  sanguinous 
pus  can  be  expressed.  The  urine  contains  albumen  and  numerous 
hyalin  casts.  The  blood  is  pale;  count  gives  leucocytes  825,000, 
erythrocytes,  2,900,000.  Differential  count,  myelocytes,  50  per  cent; 
polynuclear  and  transitional  cells,  30  per  cent;  mono-  and  polynuclear 
eosinophiles,  8  per  cent;  cells  of  lymphoid  type,  12  per  cent;  numerous 
nucleated  red  corpuscles.  Temperature  102  degrees,  pulse  90.  During 
the  following  two  days  cough  increased,  with  considerable  dyspnea  and 
cyanosis.  Death  on  third  day. 

The  body  large,  emaciated,  slight  rigor  mortis.  General  surface  pale, 
face  somewhat  cyanotic,  oedema  of  ankles.  On  the  left  side  of  the  neck  is 
a  large,  indurated  swelling  in  which,  posterior  to  the  angle  of  the  jaw,  there 
are  several  small  ragged  openings.  On  excising  this  mass  there  is  found 
a  diffuse  purulent  infiltration  extending  through  it  and  into  the  adjacent 
tissue.  The  parotid  gland  on  the  left  side  is  infiltrated  with  pus  and 
contains  necrotic  masses. 

Skin  thin,  subcutaneous  fat  yellowish,  small  in  amount,  muscles  pale. 
Peritoneum  smooth,  contains  a  small  amount  of  yellowish  fluid.  Liver 
and  spleen  enormously  enlarged.  The  spleen  occupies  the  left  side  of 
the  abdomen  extending  from  within  the  pelvis  to  the  thorax.  The  liver 
in  the  mid-clavicular  line  extends  14  cm.  below  the  costal  border,  in  the 
middle  line  13  cm.  below  the  ensifonn  cartilage.  Diaphragm  on  right 
side  can  be  pushed  to  third  intercostal  space,  on  the  left  to  the  border 
of  the  fourth  rib.  All  the  vessels  of  abdominal  organs  greatly  enlarged, 
the  splenic  vein  1.5  cm.  in  diameter  and  filled  with  a  soft,  friable,  lilac- 
colored  clot.  The  dilated  portal  veins  contain  similar  clots. 

Both  lungs  are  slightly  adherent  posteriorly;  crepitant  for  the  most 
part,  tissue  heavier  and  denser  than  normal.  On  section  pus  can  be 
squeezed  from  bronchi  in  lower  lobes.  In  the  lower  lobes  of  both  lungs 
there  are  several  areas  of  consolidation  surrounded  by  haemorrhagic 
lung  tissue,  on  section  soft,  containing  pus  in  the  centre.  In  one  of  these 
areas  there  is  a  ragged  central  cavity  with  projecting  necrotic  edges. 

Pericardial  cavity  smooth.  Right  side  of  heart  somewhat  dilated, 
heart  otherwise  of  normal  size,  right  side  and  left  auricle  contain  soft, 
rather  friable  clots.  Valves  normal,  weight  325  grams. 

Liver  very  large,  weight  3400  grams.  The  superior  inferior  diameter 
of  right  lobe  26  cm.,  that  of  the  left  16  cm.  The  lower  border  is  thick 


TERATOID  TUMORS  189 

and  round.  Capsule  smooth  and  tense.  On  section  it  is  of  a  uniform  pale 
yellowish-brown  color.  No  nodules  are  present.  All  the  vessels  large. 
Organs  firm  but  friable. 

Spleen  is  adherent  at  a  few  points.  It  measures  28  by  18  by  9  cm. 
Weight  3100  grams.  The  capsule  is  tense  and  shows  beneath  it  numer- 
ous discrete  round  or  irregular  very  dark-red  areas  which  vary  from  2  mm. 
to  2  cm.  in  diameter.  There  are  also  on  the  surface  several  pale,  opaque 
areas  up  to  3  cm.  in  diameter  with  irregular,  sharply  circumscribed  edges 
extending  irregularly  into  the  tissue  beneath.  The  spleen  is  firm, 
homogeneous  save  for  the  areas  mentioned  and  of  a  pale  grayish-red 
color.  Several  dark-red  areas  in  the  tissue  correspond  with  those  on 
the  surface. 

The  kidneys  are  of  usual  size,  weight  290  grams,  capsule  nonadherent, 
surface  smooth.  On  section  cortex  pale,  markings  obscure.  Pelves 
and  ureters  normal. 

Gastro-intestinal  canal;  transverse  colon  and  stomach  displaced 
downward.  Intestinal  wall  thickened.  There  are  a  few  foci  of  haemor- 
rhagic  infiltration  in  the  mucosa  of  the  ileum.  No  hyperplasia  of  the 
lymphoid  tissue.  In  the  ileum,  corresponding  to  the  situation  of  the 
peyers  patch,  the  wall  is  thickened  and  shows  on  the  surface  an  irregular 
shallow  ulcer  with  a  granular  base.  Section  of  intestine  passing  through 
the  ulcer  shows  several  opaque,  apparently  caseous  areas  extending 
to  peritoneal  surface. 

The  bladder  contains  a  small  amount  of  pale  urine;  the  genitalia 
are  normal. 

The  mucous  membrane  of  mouth,  pharynx  and  larynx  pale.  Tonsils 
and  lymphoid  tissue  not  enlarged.  (Esophagus  and  trachea  normal. 
Thymus  not  perceptible. 

The  lymph  nodes,  particularly  mesenteric  and  retro-peritoneal,  are 
slightly  enlarged,  pale  and  homogeneous  on  section. 

Bone  marrowr  everywhere  of  the  same  character.  In  femur  the 
medullary  cavity  is  enlarged  and  filled  with  a  granular,  friable,  reddish, 
pale  marrow  which  when  removed  contains  no  spicules  of  bone  and  leaves 
a  smooth  internal  surface. 

Scalp  of  ordinary  thickness  save  for  slight  oedema  in  left  side  corre- 
sponding with  the  cervical  swelling.  Skull  normal.  Meninges  non- 
adherent.  Brain,  weight  1240  grams,  of  ordinary  consistency. 

Cultures  from  the  neck  and  from  the  lung  gave  numerous  colonies 
of  staphylococcus  pyogenes  aureus. 

Microscopical  examination.  Sections  from  the  tissue  below  the  ear 
show  purulent  infiltration  of  tissue  and  abscess  formation.  The  larger 
veins  are  thrombosed.  The  thrombi  are  composed  principally  of  poly- 


PATHOLOGY 

nuclear  leucocytes  with  much  fibrin.  Among  the  cells  large  mono- 
nuclear  leucocytes  can  be  distinguished.  All  of  the  smaller  blood  vessels 
are  very  greatly  dilated.  The  tissue  is  cedematous  and  there  is  a  great 
deal  of  fibrin  hi  the  tissue  interstices.  Within  many  of  the  smaller 
vessels  there  are  small,  mural  thrombi.  In  various  places  in  the  tissue 
there  are  definite  abscesses  with  softening  and  complete  disintegration 
of  the  tissue.  The  cells  in  these  abscesses  are  exclusively  polynuclear 
leucocytes.  There  also  are  masses  of  round  cocci  having  the  morpho- 
logical characteristics  of  staphylococci.  The  purulent  infiltration  ex- 
tends deeply  into  the  muscles  of  the  neck.  In  the  ducts  of  the  parotid 
gland  there  are  numerous  polynuclear  leucocytes.  Within  the  dilated 
blood  vessels  the  principal  cells  are  mononuclear  with  a  round  or  oval, 
darkly  staining  nucleus,  and  finely  granular  cytoplasm.  The  next  most 
common  variety  is  a  cell  with  an  irregular,  lobulated  nucleus  somewhat 
approaching  hi  shape  that  of  the  polynuclear  leucocyte,  the  entire  cell 
and  nucleus  being  much  larger,  the  nucleus  not  so  densely  staining.  The 
large  cells  have  an  average  diameter  of  g  p.  The  polynuclear  leucocytes 
under  the  same  conditions  of  measurement  have  an  average  diameter 
of  6  ju. 

Section  of  the  lung  through  one  of  the  small  areas  of  consolidation 
shows  a  complete  purulent  infiltration  of  the  tissue;  in  the  centre  the 
tissue  is  broken  down,  only  fragments  of  alveolar  walls  being  present. 
In  the  tissue  nuclear  fragments,  evidently  from  polynuclear  cells,  and 
larger  round  masses  of  chromatin,  seemingly  derived  from  the  nuclei  of 
the  large  cells,  are  found.  In  the  surrounding  lung  tissue  there  is  con- 
siderable haemorrhage,  much  fibrinous  exudate  and  desquamated  alveo- 
lar epithelium.  In  the  intact  lung  tissue  at  a  distance,  the  alveolar  walls 
are  very  greatly  increased  in  thickness,  due  to  dilatation  of  the  capil- 
laries which  are  closely  packed  with  cells  similar  to  those  described  in 
the  parotid  region.  There  are  very  few  polynuclear  leucocytes  among 
these  cells.  Measurements  of  the  capillaries  of  the  alveolar  wall  show 
diameters  varying  between  20  and  10  ju.  Numbers  of  nuclear  figures  are 
found  in  the  cells  within  the  capillaries. 

Sections  of  mesenteric  lymph  nodes  show  all  of  the  blood  vessels  greatly 
dilated  and  filled  with  cells  of  the  same  character  as  those  described 
above.  The  lymphoid  tissue  is  small  in  amount,  the  cells  in  the  follicles 
are  widely  separated  by  oedema,  the  germinal  centres  are  not  evident. 
All  of  the  sinuses  are  greatly  dilated.  They  contain,  in  part,  large  cells 
of  the  same  character  as  those  in  the  blood;  in  part,  large  endothelial  cells 
with  characteristic  nuclei,  which  often  contain  englobed  lymphocytes. 
These  large  phagocytic  cells  are  numerous,  many  of  them  very  large  and 
containing  crystalline  masses.  These  crystals  are  of  brownish  color. 


TERATOH)  TUMORS  191 

They  lie  sometimes  in  vacuoles  of  the  cells,  sometimes  simply  enclosed  in 
the  cytoplasm;  they  occur  both  singly  and  in  masses,  are  elongated  octa- 
hedra  and  have  an  average  length  of  6  n  and  a  width  of  i  /z  (Charcot- 
Leyden  crystals).  The  cells  containing  them  are  from  20  to  30  n  in  their 
long  diameter. 

Sections  of  liver  show  this  to  be  in  large  measure  completely  sup- 
planted by  myeloid  tissue.  Within  this  there  are  here  and  there  thin 
remnants  of  liver  cells.  There  are  a  few  areas  where  the  structure  of 
the  liver  is  preserved.  In  these  places  the  liver  cells  appear  as  a  thin 
network  between  the  greatly  dilated  sinusoids.  There  are  compara- 
tively few  red  corpuscles,  the  whole  tissue  being  myeloid.  There  are 
numerous  nuclear  figures  in  the  cells. 

The  spleen  is  homogeneous  in  character.  There  are  no  lymph  follicles. 
The  trabeculae  are  only  here  and  there  visible  and  do  not  seem  to  be  in- 
creased in  amount.  The  whole  tissue  is  composed  apparently  of  dilated 
blood  vessels  and  sinusoids  with  a  very  marked  general  and  diffuse  in- 
crease in  the  connective  tissue  reticulum. 

In  a  section  of  the  kidney  the  blood  vessels  are  dilated.  The  epithe- 
lium in  the  convoluted  tubules  is  somewhat  swollen,  more  granular  and 
oedema tous.  The  glomeruli  show  slight  thickening  of  the  capillary  walls, 
the  vessels  are  dilated  and  filled  with  the  usual  cells.  Here  and  there 
in  some  of  the  capsular  spaces  there  is  coagulated  albumin.  An  occa- 
sional hyalin  cast  is  found  in  the  tubules  of  the  pyramids.  The  glom- 
eruli are  large,  some  of  them  measuring  0.3  mm.  in  diameter,  but  averaging 
about  0.2  mm. 

In  the  ulcerated  area  of  the  ileurn  there  is  a  loss  of  substance  extend- 
ing below  the  muscularis  mucosa.  The  blood  vessels  are  very  greatly 
dilated;  between  them  there  are  masses  of  lymphoid  cells,  no  definite 
follicles,  and  a  few  areas  of  definite  caseation  with  giant  cells  and  all  the 
characteristics  of  tuberculous  tissue.  The  cellular  infiltration  extends 
down  into  and  through  the  muscular  coat.  In  one  section  there  are  two 
or  three  areas  of  caseation  with  miliary  tubercles  about  them  which 
extend  completely  through  the  muscular  coat.  Search  of  this  tissue  for 
tubercle  bacilli  failed  to  reveal  them. 

REMARKS.  This  is  a  typical  case  of  myelogenous  leukemia.  Of 
interest  is  the  staphylococcus  infection  of  the  neck  and  the  ab- 
scesses containing  only  polynuclear  leucocytes.  Of  great  interest 
also  is  the  tuberculous  ulcer  of  the  ileum.  Anatomically  this  is 
characteristic,  and  the  fact  that  tubercle  bacilli  were  not  found 
does  not  vitiate  the  diagnosis.  It  is  not  always  practicable  in 
laboratory  work  to  spend  a  sufficient  time  in  such  a  search  to  detect 


1 92  PATHOLOGY 

very  small  numbers  of  bacilli  in  tissues.  The  ulcer  is  acute  and 
represents  a  very  recent  infection  which,  like  the  staphylococcus 
infection,  was  favored  by  the  depraved  physical  condition  of  the 
individual.  There  must  have  been  also  a  great  increase  in  the  total 
amount  of  blood.  The  abscesses  in  the  lung  were  haematogenous 
in  origin  and  associated  with  the  infected  thrombi  in  the  vessels 
of  the  neck. 

A  CASE  OF  DOUBLE  CONGENITAL  TERATOMA 

White,  male  child,  born  May  i8th,  pregnancy  and  labor  normal.  A 
tumor  as  large  as  a  hen's  egg  was  situated  on  the  right  side  of  the  scrotum. 
This  gradually  increased  in  size,  and  was  removed  by  operation  June  8th. 
The  outside  of  the  tumor  is  smooth  and  oval  in  shape,  measuring  7  by 
5  cm.;  it  occupies  the  position  of  the  testicle,  and  at  one  pole  is  a  pro- 
jection identified  as  epididymis.  On  section,  consists  of  a  solid  stroma 
in  which  are  small  islands  of  cartilage  and  numerous  cysts  of  various  sizes, 
the  largest  cyst  measuring  i  cm.  in  diameter,  the  smallest  just  visible  to 
the  naked  eye.  Microscopically  there  is  a  large  amount  of  striated 
muscle  tissue  in  the  solid  portion  of  the  tumor,  the  fibres  appearing  both 
singly  and  in  masses.  The  fibres  are  of  the  adult  type  and  contain 
relatively  greater  numbers  of  nuclei  than  normal.  The  areas  of  cartilage 
are  principally  hyalin,  some  fibrous.  Newly  formed  bone,  containing 
both  osteoblasts  and  osteoclasts,  is  found.  The  stroma  in  places  con- 
tains large  numbers  of  round  and  spindle-shaped  cells,  giving  it  a  dis- 
tinctly sarcomatous  appearance.  In  other  places  there  is  a  considerable 
amount  of  fibrous  and  mucoid  tissue  between  the  cells.  All  of  the  cysts 
are  lined  with  epithelium.  In  some  the  wall  is  smooth,  in  others  there 
are  numerous  papillary  projections  extending  into  the  cavity.  The 
character  of  the  epithelium  varies.  In  some  cysts  it  partakes  of  the 
character  of  the  skin  and  in  others  of  that  of  mucous  membrane.  Some 
of  the  cysts  are  lined  with  a  single  layer  of  ciliated  epithelium.  In  one 
cyst  the  epithelial  tissue  has  the  characteristics  of  that  of  the  trachea 
and  back  of  it  are  scattered  mucous  glands  and  cartilage.  A  portion 
of  the  lining  of  one  cyst  closely  simulates  the  choroid  and  retina. 

In  January  of  the  following  year  a  swelling  appeared  in  the  right 
parietal  region.  On  examination,  a  tumor  mass  was  found  connected 
with  the  skull,  the  skin  movable  over  it.  On  January  i5th,  an  operation 
was  attempted  and  showed  a  soft  tumor  partly  covered  with  bone  and 
attached  to  the  skull.  This  was  detached  leaving  the  skull  rough  and 
bare  under  it.  The  head  at  this  time  was  enlarged.  Following  the 
operation  it  grew  rapidly  in  size  increasing  i  cm.  in  circumference  daily. 


TERATOID  TUMORS  193 

Another  operation  was  performed  and  a  large  tumor  found  inside  of  the 
skull.  The  tumor  was  not  removed  and  the  head  continued  to  enlarge 
rapidly.  Ulceration  of  the  skin  over  the  tumor  took  place  in  March,  and 
several  sinuses  appeared,  from  which  fetid  pus  was  discharged.  Death 
took  place  April  23,  nine  months  after  birth. 

At  autopsy  a  large  tumor  mass  is  found  seated  chiefly  inside  the  skull, 
but  projecting  in  numerous  places  through  it.  On  its  lower  surface  the 
tumor  is  attached  to  the  dura  mater,  in  no  place  extending  through  this. 
It  weighs  1320  grams.  It  contains  numerous  cysts,  some  filled  with 
clear,  thin  fluid,  others  with  a  thick  gelatinous  material.  In  many  of 
them  are  hairs. 

On  microscopical  examination,  structures  similar  in  character  to  those 
of  the  testicular  tumor  are  found,  but  the  nervous  tissue  is  more  fully 
represented.  In  neither  tumor  are  any  structures  found  which  simulate 
either  liver,  kidney  or  spleen.  Lymphoid  tissue  in  definite  arrangement 
and  lymphoid  vessels  are  found,  but  no  tissue  resembling  marrow. 

REMARKS.  This  is  to  be  regarded  as  a  case  of  double  teratoma. 
The  tumor  of  the  skull  can  not  be  regarded  as  a  metastasis.  In 
both  tumors  the  growth  was  rapid.  It  did  not  proceed  from  any 
one  of  the  many  elements  in  the  tumor  but  seemed  to  involve  all. 
It  is  possible  that  the  growth  was  largely  due  to  enlargement  of 
the  cysts  from  secretion  of  their  epithelium.  The  growth  of  the 
tumor  was  not  infiltrating.  It  grew  as  a  mass.  The  projections 
through  the  skull  were  chiefly  through  the  natural  openings  which 
had  not  become  closed. 

EXPERIMENT.  The  complexity  of  the  experimental  work  in 
tumors  makes  it  advisable  to  limit  the  student's  work  to  the  simple 
transplantation  of  an  inoculable  mouse  tumor.  An  affected  mouse 
is  chloroformed,  and  the  skin  over  the  tumor  laid  back  with  aseptic 
precautions.  Small  pieces  of  the  non-necrotic  part  of  the  tumor 
are  placed  in  a  special  cannula,  the  obturator  inserted  so  that  the 
tumor  makes  its  appearance  at  the  sharp  end  of  the  cannula.  The 
cannula  is  inserted  subcutaneously  at  the  posterior  end  of  the  back  of 
a  normal  mouse  and  pushed  forward  subcutaneously  until  the  point 
lies  in  the  axilla.  The  obturator  is  pushed  in  so  as  to  discharge 
the  contents  of  the  cannula,  the  skin  is  pinched  about  the  end  of 
the  cannula  and  the  instrument  slowly  withdrawn.  The  opera- 
tion is  repeated  so  as  to  inoculate  ten  mice,  and  their  condition 
observed  over  several  weeks. 


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INFECTIOUS  DISEASES 

These  are  diseases  due  to  the  entry  into  the  body  of  living  things, 
which,  growing  in  the  tissues  and  fluids  of  the  body,  produce  injury. 
The  infecting  organism  is  a  parasite  and  the  infected  body  the  host. 
Not  all  parasites  are  harmful  except  in  a  very  narrrow  sense.  Most 
of  the  surfaces  of  the  body  contain  micro-organisms  which  either 
live  as  pure  saprophytes  in  the  excretory  products  or  use  up  an 
unappreciable  amount  of  body  material.  It  is  customary  to  make 
a  distinction  between  infection  and  infestation,  applying  the  latter 
term  to  the  case  in  which  large  parasites  live  at  the  expense  of  the 
body,  but  on  the  surface,  as  the  pediculi  of  the  skin  and  the  tape 
worm  of  the  alimentary  canal.  But  there  is  no  sharp  distinction, 
for  an  organism  may  at  one  period  of  its  life  infest  a  surface,  at 
another  invade  the  tissue  as  does  the  trichinella.  Considered  in  its 
biological  aspects,  infection  is  adaptation  of  an  organism  to  the 
environment  which  the  body  of  the  host  offers.  In  certain  cases 
the  environment  is  very  narrow;  for  example,  when  an  organism  is 
parasitic  for  a  certain  species  only;  in  others  the  environmental 
adaptation  may  extend  to  a  large  number  of  genera.  The  organism 
can  be  fitted  to  a  parasitic  existence  exclusively,  or  may  find  suit- 
able conditions  for  existence  outside  the  living  body,  in  which  case 
the  parasitism  is  said  to  be  facultative.  When  the  adaptation  is 
mutual,  including  both  parasite  and  host,  the  condition  is  one  of 
symbiosis.  It  is  evident  that  this  is  the  most  favorable  condition 
for  the  parasite,  and  the  death  of  the  host  an  unfortunate  incident, 
in  that  the  particular  family  branch  of  the  parasite  which  is  living 
harmoniously  in  the  host  may  be  cut  off. 

The  infectious  diseases  form  not  only  an  important  group  in 
themselves,  but,  with  the  possible  exception  of  tumors,  all  patho- 
logical conditions  in  the  body  are  to  a  greater  or  less  extent  asso- 
ciated with  present  or  past  infections.  Whatever  the  nature  of 
the  final  disease,  death,  in  the  majority  of  cases,  is  preceded  by  and 
often  the  immediate  result  of  a  terminal  infection.  Chronic  dis- 
ease of  the  heart,  of  the  arteries,  of  the  kidneys,  of  the  brain,  often 
can  be  traced  to  an  infection. 

194 


INFECTIOUS  DISEASES  195 

The  infectious  or  pathogenic  organisms  can  be  divided  into  the 
bacteria,  the  moulds,  the  yeasts  and  the  protozoa.  Some  meta'zoan 
forms  are  found,  but  they  are  of  relative  unimportance  in  human 
pathology.  The  bacteria  form  by  far  the  most  important  group, 
if  we  consider  the  number  and  importance  of  the  diseases  which 
they  produce. 

THE  BACTERIA  according  to  form  are  divided  into  the  cocci  or 
ball-shaped,  bacilli  or  rod-shaped,  and  spirilla  or  screw-shaped 
organisms.  Certain  bacilli,  as  the  tubercle  bacilli,  may  occa- 
sionally show  branched  and  irregular  forms  instead  of  the  simple 
rod.  In  general,  the  bacteria  are  monomorphic  and  the  species 
distinct,  although  within  the  species  there  may  be  considerable 
variation.  Each  bacterium  represents  a  single  cell,  but  there  is 
no  distinct  differentiation  of  nucleus  and  cytoplasm.  It  is  prob- 
able that  the  bacteria  have  a  definite  cell  membrane  which  may 
become  swollen  to  form  a  capsule.  Such  capsule  formation  plays 
a  role  in  the  pathogenesis  in  that  it  affords  protection  to  the  bacteria. 
Capsule  formation  is  most  evident  in  bacteria  which  are  growing 
in  the  body  fluids.  Many  of  the  bacteria  can  move  actively  by 
means  of  cilia  which  may  be  attached  on  all  sides,  or  at  one  or 
both  ends.  The  investigation  of  bacterial  diseases  and  the  demon- 
stration of  bacteria  in  relation  with  the  lesions  produced,  has  been 
greatly  facilitated  by  methods  of  staining.  Most  bacteria  stain 
with  the  basic  aniline  dyes.  Complex  methods  of  staining  are 
necessary  with  certain  bacteria  and  special  staining  reactions  form 
an  important  means  of  differentiation. 

The  mode  of  reproduction  of  bacteria  is  important  in  relation  to 
infection.  The  most  common  mode  is  by  simple  division.  In 
certain  species,  spores  are  produced  which  have  a  much  greater 
resistance  than  the  simple  bacterial  cell.  Spores  are  only  pro- 
duced outside  the  animal  body  and  by  bacteria  which  are  capable 
of  saprophytic  existence.  The  production  of  spores  is  important 
in  preserving  the  life  of  bacteria  and  keeping  up  the  possibilities 
of  future  infections  under  conditions  when,  without  spore  pro- 
duction, the  species  would  die.;  e.g.,  the  bacillus  of  anthrax.  Most 
of  the  pathogenic  bacteria  are  parasitic  exclusively,  finding  suitable 
conditions  for  existence  in  the  living  body  only,  or  in  special  culture 
media  at  special  temperatures,  e.g.,  tubercle  bacillus.  Others  are 
both  parasitic  and  saprophytic,  e.g.,  anthrax  bacillus;  others,  while 


1 96  PATHOLOGY 

generally  parasitic,  may,  under  suitable  conditions,  grow  as  sapro- 
phytes, e.g.,  typhoid  bacillus;  others,  while  generally  saprophytic, 
occasionally  become  parasites,  e.g.,  tetanus  bacillus. 

Bacteria  produce  injury  by  means  of  injurious  and  soluble  sub- 
stances which  they  form.  Their  mere  physical  presence  and  the 
amount  of  material  which  they  withdraw  from  the  tissues  of  the 
host  probably  exerts  no  deleterious  effect.  These  soluble  sub- 
tances  are  called  toxins,  which  are  in  some  cases  excretory  products 
of  the  bacterial  cells.  The  toxins  pass  into  the  culture  media  in 
which  they  are  grown,  and  may  be  obtained  by  nitration  and  in  a 
purer  state  by  a  variety  of  other  methods.  Certain  bacteria,  of 
which  the  diphtheria  and  the  tetanus  bacillus  are  the  best  exam- 
ples, exert  their  pathogenic  influence  solely  by  means  of  such  toxins, 
which  are  produced  at  the  site  of  infection  and  absorbed.  Other 
organisms  when  grown  in  a  culture  medium  produce  no  dissolved 
toxic  substances,  but  the  toxic  substance,  endotoxin,  is  connected 
with  the  bacterial  cell  and  set  free  by  destruction  of  the  cell.  The 
best  example  of  this  is  found  in  the  typhoid  bacillus.  There  is 
not,  however,  a  definite  distinction  between  toxin  and  endotoxin, 
for  many  bacteria  produce  both  forms  of  poison.  These  bacterial 
poisons  possess  a  more  or  less  definite  affinity  for  certain  of  the  cells 
and  tissues  of  the  body.  The  toxin  of  the  tetanus  bacillus  pos- 
sesses such  an  affinity  for  the  central  nervous  system;  that  of  the 
diphtheria  bacillus,  for  the  lymphoid  tissue;  certain  toxins,  the 
hemolysins,  attack  the  red  and  others  the  white  corpuscles.  It  is 
probable  that  this  selective  action  is  due  to  some  peculiarity  of 
structure  of  the  toxic  molecule,  physical  or  chemical,  or  both,  which 
enables  it  to  enter  or  combine  with  the  specifically  affected  cells. 
Apart  from  both  the  toxins  and  the  endotoxins,  the  protein 
substance  of  the  bacterial  cells  may  give  rise  to  lesions.  This  sub- 
stance has  no  specific  toxic  action;  it  produces  various  degrees  of 
injury  and  exerts  a  positive  chemotactic  action  on  the  white  blood 
corpuscles.  The  lesions  which  are  produced  in  bacterial  diseases 
are  due  in  part  to  the  direct  injurious  action  of  these  toxic  sub- 
stances and  in  part  due  to  the  effect  produced  in  other  parts  of 
the  body  by  the  loss  or  perversion  of  function  of  important  organs 
which  are  the  seat  of  direct  injury. 

INFECTION  takes  place  by  the  entry  of  bacteria  from  without 
through  one  of  the  surfaces  of  the  body.  These  surfaces  are  to  a 


INFECTIOUS  DISEASES  197 

greater  or  less  degree  protected.  The  skin  is  protected  by  means 
of  the  impervious  horny  layer,  by  the  constant  surface  desquama- 
tion  and  the  cell  movement  from  within  outward.  The  protection 
is  less  complete  at  the  openings  of  the  sweat  glands  and  hair 
follicles,  particularly  the  latter,  for  the  sweat  is  not  a  good  culture 
medium  and  the  direction  of  flow  opposes  entry.  Infection  by  the 
route  of  the  hair  follicles  is  not  uncommon,  for  bacteria  may  find 
a  culture  medium  in  the  moist  debris  of  the  hair  sheath  and  can 
multiply  there  and  produce  a  primary  injury.  The  conjunctiva 
has  a  rather  high  resistance  to  infection  for  most  micro-organisms, 
the  surface  is  smooth  and  the  lacrymal  secretion  and  movement  of 
lids  offer  a  certain  amount  of  physical  protection.  Infection  here 
by  the  gonococcus,  the  diphtheria  bacillus  and  other  organisms 
is  not  infrequent.  The  nasal  passages  are  protected  chiefly  by 
motion  of  the  cilia.  Infection  of  this  surface  may  take  place  by 
diphtheria,  glanders,  leprosy,  and  influenza  bacilli,  by  the  pyogenic 
cocci,  and  probably  by  other  organisms.  Infection  of  the  middle 
ear  most  frequently  occurs  from  the  entry  of  organisms  from  the 
throat  by  way  of  the  Eustachian  tube.  The  mouth,  although 
harboring  quantities  of  organisms  and  often  pathogenic  forms, 
is  a  comparatively  rare  portal  of  entry.  Actinomycosis,  noma, 
thrush  and  occasionally  tuberculosis  may  find  a  primary  location 
in  the  mouth.  The  tonsils,  particularly  in  children,  offer  a  favor- 
able site  for  infection.  The  crypts  contain  moist  masses  of  epi- 
thelium which  afford  good  cultural  conditions  for  the  diphtheria 
bacilli  and  the  pyogenic  organisms.  The  lungs  are  protected  from 
infection  by  the  moist  surface  of  the  bronchi  and  the  strong  out- 
ward currents  produced  by  the  action  of  the  cilia.  The  increasing 
surface  area  and  the  rapid  branching  of  the  bronchial  passages 
retard  the  movement  of  the  respired  air  and  favor  the  early 
lodgment  on  the  moist  surface,  of  organisms  which  have  passed 
the  guard  of  the  nasal  passages  and  the  larynx.  The  presence  and 
situation  of  the  carbon  pigment  in  the  lungs  and  the  cases  of  in- 
fection which  take  place  show  that  these  guards  are  not  always 
effective.  The  lungs  must  be  regarded  as  a  susceptible  organ  in 
spite  of  the  abundant  blood  supply,  the  ease  with  which  emigration 
of  phagocytes  takes  place,  and  the  marked  phagocytic  power  of  the 
epithelium  lining  the  alveoli.  There  is  a  further  disadvantage  in 
infections  of  the  lung,  due  to  the  great  surface  and  the  opportunity 


I98  PATHOLOGY 

for  the  organisms  to  extend  by  means  of  the  open  communicating 
canals,  the  bronchi.  Infection  from  the  mucous  membrane  of  the 
oesophagus  is  rare,  owing  to  the  thick  epithelial  covering  and  the 
smooth  surface.  The  stomach  is  comparatively  free  from  infec- 
tion, its  principal  defence  being  the  acid  gastric  secretion.  Of  all 
of  the  surfaces  of  the  body,  the  intestinal  canal  holds  the  first 
place  as  a  portal  for  infection.  The  geni to-urinary  tract  is  almost 
the  exclusive  seat  of  infection  in  the  so-called  sexual  diseases  and 
may  be  invaded  by  a  number  of  other  organisms. 

Infection  from  the  surface  probably  takes  place  in  most  instances 
by  the  bacteria  finding,  on  the  surface,  conditions  which  permit 
their  multiplication  and  the  production  of  a  local  injury,  from 
which  point  the  further  extension  takes  place.  It  is  an  important 
question  whether  or  not  bacteria  can  penetrate  an  intact  surface, 
producing  no  lesions  there,  and  be  carried  to  other  places  by  the 
blood  and  lymphatic  vessels.  Generally,  it  is  assumed  that  this 
does  take  place,  the  organisms  passing  through  the  intact  intes- 
tinal canal.  Internal  infections  are  seen  with  intact  surfaces,  but 
it  is  difficult  to  exclude  the  presence  of  minute  and  even  micro- 
scopic lesions.  The  abundance  of  nuclear  figures  in  the  crypts  of 
Lieberkiihn  show  that  destruction  and  exfoliation  of  the  epithelial 
cells  constantly  is  taking  place  and  the  surface  may,  in  many  places, 
be  robbed  of  the  protection  afforded  by  the  single  layer  of  cells. 

Infections  from  wounds  depends  much  upon  the  character  of 
the  wound.  If  with  the  wound  pathogenic  organisms  are  placed 
within  the  tissue,  and  they  find,  in  the  necrosis  of  tissue  produced 
in  injury,  a  place  for  growth  removed  from  the  action  of  the  tissue 
fluids,  infection  easily  takes  place.  The  care  taken  in  modern 
surgery  to  bring  parts  in  perfect  apposition  and  to  avoid  constric- 
tion, which  might  result  in  necrosis,  is  of  great  importance  in 
preventing  infection.  Infection  rarely  takes  place  from  granu- 
lating surfaces;  the  abundance  of  leucocytes  on  and  close  beneath 
the  surface,  gives  protection  by  phagocytosis ;  there  is  an  abundant 
stream  of  exudation  from  within  outward,  which  acts  mechanically 
and  subjects  bacteria  to  the  destructive  action  of  the  serum. 
Pathogenic  organisms,  especially  the  pyogenic  cocci,  may  be  demon- 
strated by  culture  on  the  surface  of  perfectly  healthy  and  healing 
open  wounds.  The  most  favorable  conditions  for  wound  infection 
are  found  when  organisms  are  carried  into  the  tissue  by  the  bites 


INFECTIOUS  DISEASES  199 

of  insects.  Such  inoculations  may  be  made  in  many  places,  thus 
increasing  the  probability  of  infection. 

PHAGOCYTOSIS.  Apart  from  the  various  protective  influences  of 
the  body  surfaces  and  their  accessories,  the  most  obvious  defense 
is  by  phagocytosis.  In  almost  all  of  the  lesions  produced  by 
bacteria,  an  exudate  is  produced  with  an  abundant  emigration  of 
white  corpuscles.  Either  the  bacteria  themselves  or  the  necrotic 
tissue  produced  by  their  action,  or  both,  exert  a  positive  chemotaxis 
attracting  the  leucocytes  to  the  part.  The  wandering  cells  take 
up  the  bacteria  which  become  surrounded  in  the  cell  by  clear  fluid, 
in  which  they  are  broken  up  and  disappear.  Their  destruction  is 
a  process  of  intracellular  digestion.  The  leucocytes  which  are 
chiefly  concerned  in  such  bacterial  destruction  are  the  polynuclear. 
Phagocytosis  by  endothelial  cells,  both  those  of  the  blood  and  those 
formed  in  the  tissues,  takes  place,  but  to  a  far  less  extent.  It 
never  takes  place  in  cells  of  the  lymphoid  series.  It  has  been 
shown  that  phagocytosis  is  facilitated  by  some  alteration  produced 
in  the  bacteria  by  the  action  of  substances  called  opsonins,  which 
are  present  in  the  blood  and  which  are  capable  of  increasing  in 
amount  during  the  course  of  an  infection.  The  presence  of  bacteria 
within  polynuclear  leucocytes  is  not  in  itself  a  certain  indication 
of  phagocytosis.  The  gonococci,  for  instance,  seem  to  find  in  the 
polynuclear  leucocytes  the  conditions  for  existence  and  growth, 
and  there  is  no  evidence  of  their  destruction.  It  is  also  by  no 
means  certain  that  the  tubercle  bacilli  which  so  often  are  found 
enclosed  in  endothelial  cells  or  hi  giant  cells  are  destroyed. 

BACTERIOLYSIS.  The  bacteria  also  are  destroyed  by  the  action 
upon  them  of  soluble  bactericidal  substances  contained  hi  the 
blood.  Such  destruction  is  effected  by  the  interaction  of  two 
substances,  one  of  which  hi  itself  is  inoperative,  but  the  action  of 
which  is  necessary  in  order  that  the  substance  which  produces  the 
destruction  may  act.  This  sensitizing  substance  is  known  as  the 
amboceptor,  the  destructive  substance  as  the  alexine  or  comple- 
ment. The  separate  action  of  these  two  substances  can  easily  be 
tested  since  the  amboceptor  is  thermolstabile  and  is  not  destroyed 
by  a  temperature  of  56  degrees,  while  the  complement  is  thermo- 
labile  and  is  destroyed  by  this  temperature.  The  amboceptor 
probably  is  produced  by  the  tissue  cells;  its  amount  may  increase 
in  the  course  of  infection  and  its  formation  be  stimulated.  The 


200  PATHOLOGY 

action  of  the  amboceptor  is  specific.  The  presence  of  an  ambo- 
ceptor  enables  the  complement  to  act  on  one  species  of  bacterium 
but  not  on  another. 

ANTITOXINS.  It  has  been  seen  that  certain  of  the  bacteria  have 
little  tendency  to  invade  the  tissues,  but  act  by  the  production  of 
toxic  substances  which  are  absorbed  and  have  a  specific  influence 
on  certain  tissues  of  the  body.  Against  the  action  of  such  toxins 
the  body  cells  react  by  the  formation  of  antitoxins  which  neu- 
tralize or  destroy  the  toxins.  The  formation  of  these  antitoxins 
may  be  brought  about  by  the  injection  into  an  animal  of  toxins 
formed  by  the  growth  of  the  bacteria  outside  of  the  body.  Such 
antitoxins  have  no  injurious  action  on  the  bacteria  themselves. 
Phagocytosis,  bacteriolysis,  and  the  neutralization  of  toxin  by 
antitoxin  will  take  place  outside  of  the  body  in  the  test  tube. 
The  action  involved  in  the  destruction  of  bacteria  is  a  general 
action,  and  takes  place  when  any  foreign  cells  are  introduced  into 
the  body.  It  has  been  most  studied  and  the  clearest  ideas  have 
been  formed  concerning  it,  in  the  reaction  of  an  animal  to  the  in- 
jection of  foreign  red  corpuscles.  The  hemolysis  or  destruction  of 
the  foreign  corpuscles  is  effected  by  the  interaction  of  amboceptor 
and  complement,  and  by  the  injection  of  the  foreign  corpuscles  in 
small  numbers  the  amount  of  amboceptor  can  be  greatly  increased. 
Any  substance  which  gives  rise  to  the  formation  of  antibodies  is 
called  an  antigen. 

LESIONS  PRODUCED.  The  different  organs  of  the  body  show 
great  variations  in  the  lesions  produced.  The  best  example  of 
this  is  seen  in  tuberculosis.  The  skin  offers  a  high  degree  of  re- 
sistance to  the  action  of  the  bacilli.  The  lesions  produced  are 
slow  in  development,  circumscribed  in  character,  there  is  but 
feeble  growth  of  the  organisms,  and  there  is  but  little  tendency  to 
the  degenerations  so  commonly  associated  with  the  action  of  the 
bacilli.  The  liver,  while  highly  susceptible  to  attack,  quickly 
acquires  a  high  resistance,  in  it  the  lesions  are  numerous,  circum- 
scribed in  character,  and  the  bacilli  so  few  that  their  demonstration 
is  difficult.  The  voluntary  muscles  possess  an  almost  complete 
immunity.  The  streptococcus  infections  of  the  skin  also  differ  in 
character  from  infections  elsewhere.  Erysipelas  has  the  charac- 
teristics of  a  specific  infectious  disease  with  a  constant  cause, 
lesions  of  the  same  character  and  a  definite  clinical  course;  yet 


INFECTIOUS  DISEASES  201 

presumably  the  same  streptococcus  which  causes  the  erysipelas 
produces  in  the  lungs,  or  in  the  uterus,  or  in  the  peritoneum,  a 
totally  different  process. 

NATURAL  IMMUNITY.  It  has  been  known  and  experimentally 
demonstrated  that  certain  animal  species  are  immune  or  resistant 
to  the  action  of  organisms  to  which  other  animals,  and  even  species 
closely  related,  are  susceptible.  Under  natural  conditions  the 
mode  of  life  may  not  favor  infection,  which  seems  to  be  the  cause 
for  the  infrequency  of  tuberculosis  in  susceptible  animals  in  a  feral 
state.  The  immunity  may  depend  upon  peculiarities  of  anatomical 
structure  which  offer  a  passive  resistance  to  infection.  Apart  from 
such  considerations  under  the  most  favorable  conditions  for  in- 
fection the  disease  may  not  be  acquired.  This  is  due  to  the  fact 
that  in  the  body  of  the  animal,  resistant  and  bacterial  destructive 
substances  are  either  already  present  or  easily  formed.  It  has 
been  found  that  phagocytic  destruction  of  bacteria  more  easily 
takes  place  in  the  resistant  animal.  There  may  be  a  high  degree 
of  natural  resistance  to  the  action  of  bacterial  toxins,  due  either 
to  the  presence  of  a  neutralizing  antitoxic  substance  in  the  blood, 
or  to  the  fact  that  the  toxin  is  not  able  to  act  on  the  cells,  or  the 
toxin  may  have  a  special  affinity  for  the  cells  of  some  non-essential 
tissue.  The  toxin  immunity  may  not  be  absolute.  The  horse 
has  the  greatest  susceptibility  to  the  action  of  tetanus  toxin.  If 
the  minimal  fatal  dose  for  one  gram  of  of  horse  weight  be  taken  as 
a  unit,  the  scale  of  resistance  for  some  other  animals  is  as  follows: 
for  i  gram  of  guinea  pig,  2  units  are  fatal;  i  gram  of  goat,  4  units; 
i  gram  of  mouse,  13  units;  i  gram  of  rabbit,  2000  units;  i  gram  of 
chicken,  200,000  units. 

SUSCEPTIBILITY.  Variations  in  individual  susceptibility  are 
difficult  to  estimate.  The  fact  that  certain  individuals  in  epi- 
demics, in  spite  of  apparent  exposure  to  infection,  do  not  acquire 
the  disease  may  be  in  large  degree  due  to  accident.  There  is  no 
immunity  of  tissues  to  the  action  of  bullets  and  yet  most  soldiers 
go  through  battle  untouched.  Immunity  may  have  been  acquired 
by  previous  infections  which  were  not  recognized.  It  is  even  not 
inconceivable  that  immunity  may  be  acquired  by  an  infection 
which  does  not  become  evident,  immunity  being  developed  during 
the  stage  of  incubation  and  before  constitutional  disturbance 
appeared.  The  resistance  of  individuals  may  be  lowered  in  a 


aoa  PATHOLOGY 

variety  of  ways.  Experimentally,  it  has  been  shown  that  hunger, 
extreme  fatigue,  prolonged  narcosis,  refrigeration,  will  increase 
animal  susceptibility,  and  in  man  famine  and  pestilence  go  hand 
in  hand.  A  previous  disease  may  render  infection  more  probable. 
This  is  seen  not  only  in  the  secondary  infections,  but  in  the  fre- 
quency with  which  infectious  diseases  follow  one  another.  The 
very  ill  understood  condition  of  taking  cold,  or  refrigeration,  makes 
infection  more  probable,  and  chronic  alcoholism  increases  both 
the  frequency  and  severity  of  certain  infections  such  as  pneumonia. 
All  of  these  conditions  may,  in  various  ways,  so  affect  the  nutrition 
and  vitality  of  the  cells  that  they  no  longer  react  with  the  same 
energy.  Age  has  an  influence  on  infection.  Certain  diseases  are 
known  as  the  diseases  of  childhood  and  it  is  assumed  that  this  is 
because  of  greater  susceptibility  on  the  part  of  the  young.  Chil- 
dren, however,  represent  raw  material  without  immunity  conferred 
by  previous  attacks.  In  the  pre-vaccination  period,  smallpox  was 
preeminently  a  disease  of  childhood  although  all  ages  probably 
are  equally  susceptible.  The  period  at  which  children  are  most 
susceptible  to  infectious  disease  is  during  the  school  age  when  the 
close  association  gives  better  opportunity  for  infection.  Children 
are  more  susceptible  to  secondary  infections,  particularly  those 
caused  by  streptococci,  than  are  adults.  This  is  shown  by  the 
frequency  of  broncho-pneumonia  and  otitis  media.  They  also  are 
more  susceptible  to  infections  of  the  alimentary  canal.  It  is  un- 
certain whether  this  depends  upon  conditions  favoring  the  entry 
of  organisms  or  upon  absence  of  the  general  mode  of  defense. 

THE  INTERACTION  BETWEEN  THE  TISSUES  AND  THE  INFECTING 
ORGANISMS  is  well  shown  in  staphylococcus  infection.  When  the 
cornea  of  a  rabbit  is  inoculated  with  a  culture  of  staphylococcus 
aureus,  the  organisms  grow  in  the  cell  spaces  of  the  tissue  forming 
masses  conforming  to  these,  the  entire  mass  of  organisms  being 
compact.  The  vessels  of  the  surrounding  conjunctiva  and  the 
scleral  vessels  at  the  edge  of  the  cornea  become  congested;  emi- 
gration of  polynuclear  leucocytes  takes  place  rapidly  and  the  emi- 
grated cells  pass  through  the  tissue  forming  a  compact  wall  around 
the  bacteria,  not  only  the  cell  spaces  but  the  interfibrillar  tissue 
also  being  filled  with  them.  This  wall  of  leucocytes,  however,  is 
not  formed  immediately  around  the  masses  of  bacteria,  but  an 
area  of  completely  necrotic  tissue  intervenes  between  the  bacteria 


INFECTIOUS  DISEASES  203 

and  the  leucocytes.  The  advance  of  the  leucocytes  is  halted  at  a 
distance  from  the  masses  of  cocci.  Not  only  is  their  progress 
halted,  but  the  necrosis  which  has  taken  place  hi  the  corneal  tissue 
extends,  to  some  extent,  to  the  leucocytes.  Such  a  wall  of  leuco- 
cytes in  itself  forms  a  protection  in  limiting  the  advance  of  the 
bacteria  and  probably  in  limiting  and  opposing  the  action  of  the 
destructive  substances  which  they  produce.  The  next  process  is 
the  liquefaction  of  the  tissue  around  the  bacteria  and  the  advance 
of  the  leucocytes.  The  liquefaction  of  the  tissue  is  due  to  pro- 
teolytic  ferments,  the  production  of  which  is  a  property  especially 
marked  in  the  pus  producing  bacteria.  In  the  cornea  the  lique- 
faction and  leucocytic  advance  go  together;  in  other  tissues  the 
leucocytes  gain  resistance  to  the  necrotic  or  paralyzing  action  of 
the  bacterial  substances,  and  advance  before  the  histolysis  of  the 
necrotic  tissue  takes  place.  The  formation  of  this  definite  cir- 
cumscribed wall  of  necrotic  tissue  which  at  first  forms  a  bar  to  the 
leucocytes  is  one  of  the  most  striking  features  of  abscess  formation. 
When  staphylococci  are  injected  into  the  ear  vein  of  a  rabbit,  the 
cocci  find  lodgment  within  the  vessels  at  various  places,  particularly 
in  the  heart  and  the  kidneys.  They  multiply,  form  masses  occlud- 
ing the  vessels,  and  around  each  mass  the  same  process  takes  place 
as  in  the  cornea.  There  is  no  immediate  phagocytosis,  but  before 
this  takes  place  there  is  either  a  neutralization  or  destruction  of  the 
necrotizing  substance  or  the  action  of  opsonins  on  the  bacteria 
stimulating  phagocytosis,  or  both.  With  the  histolysis  of  the 
tissue  an  ulcer  is  produced  on  the  cornea;  an  abscess,  when  the 
process  is  within  the  tissues.  Destruction  of  cocci  both  by  phago- 
cytosis and  bacteriolysis  proceeds  rapidly.  The  healing  of  both 
the  ulcer  and  the  abscess  is  brought  about  by  the  formation  of 
granulation  tissue. 

The  production  of  necrosis  of  tissue  around  bacteria  is  not  a 
common  property.  Masses  of  typhoid  and  other  bacteria  may  be 
found  in  the  tissue  without  necrosis,  nor  is  leucocytic  reaction 
always  present.  In  general,  however,  the  lesions  associated  with 
the  presence  of  bacteria  in  the  tissue  are  of  inflammatory  character. 
In  certain  cases  the  tissue  reactions  are  so  characteristic  and  so 
specific  that  from  them  the  nature  of  the  infection  can,  with  great 
but  not  absolute  certainty,  be  determined.  The  tissue  reaction 
characteristic  of  a  special  organism  does  not,  however,  always  take 


204  PATHOLOGY 

place.  The  tubercle  is  one  of  the  most  characteristic  of  the  products 
of  bacterial  action,  but  the  tubercle  bacilli  may,  in  certain  cases, 
produce  suppuration  or  fibrino-purulent  exudation. 

ATRIUM  OF  INFECTION.  Bacteria  usually  produce  a  local  lesion 
at  the  point  of  entry  which  is  called  the  infection  atrium.  From 
this  they  may  extend  further  into  the  body  by  means  of  the  lym- 
phatics or  by  the  blood,  producing  metastases.  The  situation  of 
the  metastases  is  determined  by  many  factors,  the  most  important 
of  which  probably  are  the  varying  degrees  of  resistance  in  the 
different  organs  of  the  body.  Certain  organs  have  a  high  degree 
of  resistance  to  bacterial  action  in  general  as  the  tissue  of  the 
brain,  the  muscle,  the  testicle  and  the  ovary.  The  presence  of 
metastases  in  certain  organs  may  be  determined  by  the  character 
of  the  organism;  for  example,  the  metastases  in  the  muscles  and 
testicle  in  glanders,  the  bacillus  mallei  apparently  finding  in  these 
organs  the  most  suitable  environment  for  multiplication.  The 
blood  must  be  regarded  as  a  resistant  organ.  In  every  infection 
it  is  probable  that  organisms  enter  the  blood  by  means  of  the  lym- 
phatics, some  organisms  passing  through  the  barriers  of  the  lymph 
nodes,  or  by  means  of  blood  vessels  with  or  without  a  preceding 
formation  of  thrombi.  The  entering  organisms  may  be  destroyed 
in  the  blood,  or  this  may  act  simply  as  a  carrier  by  means  of  which 
the  organisms  are  deposited  in  other  places;  in  still  other  cases  the 
organisms  may  survive  or  even  grow  in  the  blood,  the  condition  being 
known  as  bacteraemia.  The  best  example  of  bacteraemia  is  seen  in 
anthrax  or  in  pneumococcus  infection  in  highly  susceptible  animals. 

CHRONIC  INFECTIONS.  Infections  by  some  organisms  tend  to 
pursue  a  chronic  course.  Tuberculosis  and  leprosy  may  be  taken 
as  the  types  of  such  chronic  diseases.  In  the  case  of  tuberculosis 
the  bacillus  is  of  slight  virulence  and  ordinarily  of  little  power  of 
growth  in  the  body.  The  lesions  produced  as  a  rule  are  circum- 
scribed and  extend  slowly  by  infection  of  adjacent  tissue.  The 
formation  of  connective  tissue  is  stimulated  and  the  areas  of  dis- 
ease may  become  surrounded  by  dense  capsules  of  connective 
tissue  which  act  as  a  protection  against  further  advance.  The 
organisms  persist  in  the  areas  and  further  infections  occur  at  in- 
tervals. In  other  chronic  infections  the  organisms  may  collect 
in  certain  organs,  as  in  the  spleen,  and  from  these  depots  further 
invasion  occurs.  Each  onset  may  be  met  by  the  creation  of  a 


INFECTIOUS  DISEASES  205 

temporary  general  immunity  which  does  not  extend  to  the  destruc- 
tion of  the  organisms  in  the  isolated  depots.    In  the  acute  infec- 
tions, on  the  other  hand,  the  resistance  of  the  body  increases  to  an 
extent  which  brings  about  destruction  of  the  infecting  organisms, 
resulting  in  recovery  or  death  from  the  inadequacy  of  resistance. 
PERIODS  OF  INFECTIOUS  DISEASE.    In  many  of  the  infectious 
diseases  there  is  a  period  between  the  attack  of  the  organism  and 
the  appearance  of  constitutional  evidence  of  the  disease  which  is 
called  the  period  of  incubation.     It  is  variable  in  the  different  in- 
fections and  may  vary  in  different  cases  of  the  same  infection. 
In  certain  infections,  as  in  smallpox,  it  is  dated  from  the  oppor- 
tunity for  infection,  and  the  disease  appears  almost  invariably 
twelve  days  after  this.     In  certain  cases  the  period  is  terminated 
gradually,  the  constitutional  symptoms  slowly  appearing;  and  in 
others,  the  best  example  being  smallpox,  the  termination  is  sudden. 
Nothing  in  the  infectious  diseases  is  so  uncertain  as  our  knowledge 
of  what  is  taking  place  during  the  period  of  incubation.     In  those 
infections  in  which  there  is  a  well-marked  infectious  atrium  or 
primary  lesion,  it  seems  evident  that  during  this  period  the  or- 
ganisms are  multiplying  and  producing  toxins  hi  the  focal  infec- 
tion, and  the  constitutional  disturbances  begin  when  a  sufficient 
amount  of  toxin  has  been  produced.     The  defensive  forces  of  the 
blood  may  at  first  be  sufficient  to  neutralize  toxins  and  to  destroy 
bacteria;  the  constitutional  disturbance  appears  when  the  defenses 
of  the  body  are  overcome.     It  is  not  even  necessary  that  there 
should  be  a  local  infection,  for  the  bacteria  may  find  opportunity 
for  growth  on  some  one  of  the  surfaces  and  there  produce  the  toxic 
substances,  the  absorption  of  which  produces  the  constitutional 
disturbance.     In  smallpox,  in  scarlet  fever  and  in  typhoid  fever 
no  such  primary  infections  have  been  found.     In  most  infections, 
there  follows  the  period  of  incubation,  a  period  in  which  the  signs 
and  symptoms  of  the  disease  develop,  the  period  of  invasion.    The 
symptoms  may  develop  rapidly,  frank  invasion,  or   insidiously. 
The  acme  of  the  disease  or  fastigium  may  be  slowly  or  rapidly 
attained.    This  is  followed  by  defervescence  or  decline  which  may 
take  place  rapidly  (crisis)  or  slowly  (lysis).    The  period  of  con- 
valescence, during  which  the  patient  returns  to  a  normal  state, 
follows  the  decline.     These  conditions  are  best  seen  in  the  acute 
infectious  diseases,  such  as  pneumonia  and  typhoid  fever. 


206  PATHOLOGY 

RECOVERY  takes  place  when  the  body  has  acquired  the  power  of 
destroying  the  organisms  and  neutralizing  their  toxins.  When  in 
diphtheria  the  toxins  are  neutralized  by  the  antitoxins,  not  only 
is  the  toxic  action  on  internal  organs  prevented,  but  the  concen- 
trated toxins  associated  with  the  bacilli  on  the  mucous  surface 
are  no  longer  able  to  produce  the  epithelial  necrosis  and  fibrinous 
exudation  which  give  the  best  conditions  for  bacterial  growth. 
The  bacteria  can  exist  for  a  long  time  as  saprophytes  on  the  mucous 
surface,  but  no  longer  are  capable  of  injury.  The  bacteria  which 
invade  the  body  are  destroyed  both  by  phagocytosis  and  by  bac- 
teriolysis. In  any  case  recovery  from  an  infection  means  that  the 
body  is  immune  to  the  action  of  the  infecting  organism.  In  certain 
cases  the  immunity  is  local  only,  as  in  staphylococcus  infection; 
infection  in  a  locality  adjacent  to  the  focus  which  has  become 
immune  to  the  organism  can  take  place,  as  is  seen  in  the  frequent 
new  infections  around  a  furuncle.  In  this  case  there  has  been  no 
general  invasion  of  the  body  resulting  in  a  general  increase  of 
defensive  powers,  but  both  the  attack  by  the  bacteria  and  the 
defense  by  phagocytosis,  chiefly  have  been  local.  The  general 
immunity  always  lasts  for  a  period  which,  in  some  infections,  ex- 
tends through  the  life  of  the  individual.  Such  immunity  depends 
upon  the  cells  retaining  the  power,  on  the  reception  of  the  specific 
stimuli,  of  producing  specific  antibodies.  The  exercise  of  definite 
functions  by  the  cells  increases  the  facility  of  performance. 

REMOVAL  OF  ORGANISMS.  Bacteria  are  discharged  from  the 
infected  individuals  not  only  when  lesions  communicate  with 
surfaces,  but  they  may  be  discharged  through  secretory  channels. 
In  typhoid  fever  the  bacilli  are  discharged  by  the  urine  and  bile, 
in  hydrophobia  the  virus  (of  an  unknown  nature)  through  the 
salivary  glands;  cholera  and  dysentery  organisms  when  injected 
into  the  blood  appear  in  the  alimentary  canal.  This  is  not  a 
process  of  secretion;  the  bacilli  produce  small  lesions  in  the  tissue 
by  which  they  enter  the  ducts  and  are  conveyed  into  the  urine  and 
bile  in  which  places  they  find  opportunities  for  growth.  They  may 
persist  in  the  cavities  for  some  time  and,  in  the  case  of  the  gall 
bladder,  for  years  after  the  disease  is  recovered  from  causing  the 
affected  individuals  to  act  as  "carriers." 

HEREDITARY.  Hereditary  transmission  of  infectious  disease 
cannot  occur,  for  the  factors  in  heredity  are  concerned  with  germ 


INFECTIOUS  DISEASES  207 

plasm;  an  infectious  organism,  if  present,  would  be  a  case  of  germ 
cell  infection  and  not  of  hereditary  transmission.  The  ova  can 
become  infected  and  the  infection  extend  to  the  embryo,  but 
infection  of  the  spermatozoon,  if  it  occurs  at  all,  must  be  very  infre- 
quent. Germinal  infection  of  the  ova  occurs  in  insects,  particu- 
larly in  ticks,  but  it  is  uncertain  that  it  ever  occurs  in  man. 

INTRA-UTERINE  INFECTION.  Infection  of  the  embryo  or  fetus  by 
the  mother,  by  way  of  the  placenta,  has  been  demonstrated  experi- 
mentally, and  in  man  has  been  shown  in  syphilis,  in  typhoid  fever, 
in  tuberculosis  and  in  small-pox.  It  may  take  place  either  with  or 
without  the  production  of  a  focus  of  infection  in  the  placenta. 
In  certain  cases  no  lesions  of  the  placenta  have  been  found,  but 
to  disprove  the  existence  of  minute  lesions  would  be  well  nigh 
impossible.  The  presence  in  the  placenta  of  foci  of  necrosis,  which 
is  very  common,  would  favor  infection  by  giving  bacteria  places 
for  growth  where  they  would  be  removed  from  the  action  of  the 
blood. 

SECONDARY  INFECTION,  that  is,  an  infection  by  an  organism 
different  from  that  producing  the  primary  infection,  plays  an  im- 
portant part  in  the  infectious  diseases.  The  secondary  organism 
may  find  entrance  into  the  body  through  lesions  produced  in  the 
primary  disease,  as  in  the  case  of  infection  by  streptococci  through 
the  areas  of  ulceration  in  the  lungs  produced  by  the  tubercle  bacilli. 
The  resisting  powers  of  the  body  may  be  so  weakened  in  the  first 
infection  that  the  secondary  infection  may  be  but  little  opposed. 
By  the  indefinite  term  of  weakening  of  resistance  must  be  under- 
stood in  a  general  way  an  inability  of  the  body  to  produce  those 
substances  on  which  immunity  and  resistance  depend.  The  bone 
marrow  may  share  in  the  general  injury  produced  by  the  first 
infection  and  not  only  phagocytosis,  but  the  reactive  leucocytosis 
be  inhibited.  In  some  of  the  most  typical  of  the  infectious  diseases 
death,  in  most  cases,  is  to  be  attributed  not  to  the  primary  cause, 
but  to  the  secondary  infection.  The  streptococcus  is  the  most 
common  organism  of  secondary  infection,  and  the  lungs  the  most 
frequent  atrium  of  infection. 

TERMINAL  INFECTIONS  are  infections  which  occur  shortly  before 
death.  Cultures  from  organs  at  autopsies  frequently  show  various 
pathogenic  organisms  in  the  blood  or  in  organs  where  they  could 
only  be  carried  by  the  blood  circulation.  There  may  be  no  lesions 


20S  PATHOLOGY 

in  the  tissues  associated  with  the  organisms,  or  lesions  of  slight 
development. 

VARIATIONS  IN  INFECTIONS.  The  great  differences  which  in- 
fections show  in  severity,  in  character  and  extent  of  lesions  and  of 
distribution  in  the  body,  depend  upon  a  number  of  factors.  In 
the  infection  there  is  an  interaction  of  two  organisms  and  the 
enormous  variability  of  living  matter  in  such  an  interaction  would 
of  itself  produce  differences  in  result.  However  nearly  the  same 
conditions  can  be  approached  in  experimental  infections,  the  result 
is  not  always  the  same.  If  susceptible  animals  of  the  same  litter 
and  weight  be  inoculated  with  an  infectious  organism  which  has 
been  shown  to  be  fatal  for  the  species,  the  interval  before  death 
varies  and  if  a  less  virulent  organism  be  used  some  of  the  animals 
will  die,  some  recover  and  in  some  there  may  be  little  or  no  result. 
In  this  experiment  the  conditions  on  the  side  of  the  infecting  or- 
ganisms are  uniform  for  it  may  be  assumed  that  in  the  large  number 
of  organisms  used  for  inoculation  and  taken  from  the  same  culture, 
average  conditions  will  be  found.  In  the  natural  infections  the 
differences  are  more  marked  because  more  factors  enter.  There 
may  here  be  differences  due  to  variations  in  virulence  of  the  in- 
fecting organism  and  in  the  number  which  enter,  and  on  the  part 
of  the  body  variations  in  the  general  resistance  and  in  the  resist- 
ance of  the  particular  tissue  or  organ  affected.  Different  cultures 
of  the  same  organism  vary  in  their  power  to  produce  disease  in 
animals.  The  infectious  power  or  pathogenicity  can  be  increased 
by  passing  the  organism  through  the  more  susceptible  animals  or 
by  growing  them  in  collodion  sacs  placed  in  cavities  in  the  animals 
so  that  the  growing  organisms  come  in  contact  with  the  tissue 
fluids;  it  can  be  diminished  by  constant  growth  in  the  test  tube, 
by  action  of  light,  by  variations  in  temperature,  by  the  action  of 
chemical  substances.  Virulence  in  an  organism  depends  upon  two 
factors,  the  power  of  growth  and  the  power  to  produce  toxic  sub- 
stances, the  two  conditions  sometimes,  but  not  always,  acting 
together.  The  organism  growing  withjn  the  body  acquires  im- 
munity to  the  inhospitable  activities  of  the  host,  and  may  transmit 
the  acquired  immunity  to  successive  generations  in  the  same  way 
that  the  cells  of  the  host  acquire  immunity  and  transmit  it  to  suc- 
cessive generations  of  cells.  In  the  same  disease,  as  in  tubercu- 
losis, we  find  in  one  case  great  numbers  of  bacilli  which  produce 


INFECTIOUS  DISEASES  209 

little  reaction  in  the  tissues  about  them,  and  in  another  case  ex- 
tensive tissue  lesions  associated  with  small  numbers  of  organisms. 
The  leprosy  bacilli  have,  at  times  certainly,  enormous  power  of 
growth  and  produce,  in  relation  to  their  numbers,  lesions  of  slight 
extent,  while  the  tetanus  bacilli  have  but  feeble  power  of  growth 
but  great  toxicity.  In  experimental  infections  quantity  or  doses 
of  organisms  required  to  produce  infection  vary  with  different 
species  and  with  different  strains.  Certain  organisms  are  so  highly 
infectious  that  a  single  individual  may  infect  an  extremely  sus- 
ceptible animal,  as  anthrax  in  mice;  but  in  general  greater  numbers 
are  required.  How  much  the  number  of  organisms  entering  the 
body  influence  infections  in  man  is  uncertain. 


THE  SPECIAL  INFECTIONS 

It  would  be  possible  to  make  a  classification  of  the  infections 
according  to  the  type  of  tissue  lesions  produced  in  each,  but  the 
action  of  the  bacteria  varies  so  much,  is  affected  by  so  many  con- 
ditions, that  such  a  classification  is  artificial.  Suppuration,  for 
instance,  is  most  frequently  produced  by  the  pyogenic  bacteria, 
but  a  number  of  organisms,  which  ordinarily  exert  a  toxic  action, 
or  which  produce  lesions  of  the  character  of  tubercles,  may,  under 
conditions  which  are  imperfectly  understood,  produce  typical 
suppuration,  and  the  pyogenic  cocci  may  not  act  in  the  way  usual 
for  them. 


STAPHYLOCOCCUS   AUREUS 

This  is  a  coccus  which,  both  in  cultures  and  in  the  tissues,  tends 
to  occur  in  clumps  and  masses.  It  grows  on  all  of  the  usual  labora- 
tory media  and  produces  a  golden-yellow  pigment.  It  is  widely 
distributed  and  the  ease  with  which  it  grows  and  the  wide  tem- 
perature limits  of  growth,  10°  to  40°  C.,  makes  saprophytic  growth 
possible.  There  is  an  endotoxin  combined  with  the  bodies  of  the 
cocci  and  growing  in  cultures  it  produces  a  hemolysin  and  leuco- 
cidin.  It  also  produces  a  proteolytic  ferment  and  liquefies 
gelatine.  The  virulence  of  different  strains  of  the  organism  varies 
greatly  and  the  virulence  is  increased  by  passage  through  animals. 

The  susceptibility  of  animals  to  infection  by  this  organism  varies 
greatly  both  as  to  species  and  individuals,  and  on  the  whole  they 
seem  less  susceptible  than  man.  Of  the  common  laboratory  ani- 
mals rabbits  are  the  most  susceptible.  Infection  by  the  staphyl- 
ococcus  is  greatly  favored  by  the  presence  of  a  focus  in  which  the 
organisms  can  grow  removed  from  the  action  of  the  tissue  fluids 
and  where  they  are  prevented  from  passing  into  the  blood.  In- 
jection of  a  bouillon  culture  of  the  organisms  into  the  peritoneal 
cavity  of  a  dog  may  produce  no  effect,  but  if  a  portion  of  potato  or 
agar  culture  is  placed  in  the  cavity  peritonitis  results. 

The  staphylococcus  is  the  typical  pyogenic  organism.  Circum- 
scribed abscesses  in  the  tissue  are  more  often  produced  by  this  than 
by  any  other  organism.  The  first  effect  of  the  organism  is  the  pro- 
duction of  an  area  of  necrosis  in  the  tissue  surrounding  it.  It  has 
a  marked  positive  chemotaxis  for  the  polynuclear  leucocytes  and, 
by  means  of  the  proteolytic  ferment  which  it  produces,  the  inter- 
cellular substances  are  dissolved  and  a  cavity  formed  in  the  tissue 
containing  leucocytes,  cell  and  tissue  detritus,  and  organisms. 
The  wall  of  the  cavity  is  filled  with  leucocytes  and  a  dense  granu- 
lation tissue  is  formed.  This  is  the  pyogenic  membrane  from  which 
leucocytes  continually  pass  into  the  cavity.  The  tension  of  the 
pus  in  the  cavity  may  exceed  the  tension  in  the  surrounding  tissue. 
The  abscess  may  extend  to  a  surface,  by  the  continuance  of  the 
tissue  liquefaction  aided  by  the  tension  of  the  contents,  and  dis- 

211 


212  PATHOLOGY 

charge.  On  the  surface  of  the  body  this  is  favorable,  but  if  the 
discharge  of  the  abscess  into  a  body  cavity  takes  place,  the  infection 
extends  to  this.  Healing  takes  place  by  the  destruction  of  the 
organisms  by  phagocytosis  and  the  tissue  loss  is  made  good  by 
the  usual  processes  of  repair  and  regeneration.  Local  immunity, 
due  to  a  local  defense  by  phagocytosis  and  adaptation  of  tissue  to 
toxic  action  or  the  greater  resistance  of  the  granulation  tissue 
which  replaces  the  parenchyma,  may  be  produced  without  any 
general  immunity.  The  greater  the  virulence  of  the  organism  the 
less  may  be  the  local  reaction.  A  general  leucocytosis  is  a  part 
of  the  infection.  There  is  less  tendency  for  the  extension  of  the 
infection  by  means  of  lymphatics  and  blood  than  in  the  case  of 
the  streptococcus  infections.  In  the  formation  of  the  abscess  but 
little  fibrin  is  formed  and  this  undergoes  liquefaction.  When  the 
infection  of  a  serous  surface  results  the  exudation  may  contain 
large  amounts  of  fibrin. 

PRINCIPAL  LESIONS  PRODUCED.  Furuncle  and  carbuncle:  A 
furuncle  is  a  local  necrosis  and  suppuration  of  the  corium  due  to 
infection  of  a  hair  follicle.  The  organism  grows  in  the  contents 
of  the  follicle  and  produces  necrosis,  which  extends  with  the  multi- 
plication of  the  cocci.  The  dense  tissue  of  the  corium  is  resistant 
to  liquefaction  and  the  necrotic  tissue  forms  a  hard  mass,  the  so- 
called  core  of  the  furuncle.  In  the  carbuncle  the  necrosis  is  more 
extensive  and  may  involve  the  subcutaneous  tissue  and  fascia  and 
several  openings  may  appear  in  the  skin  over  the  area.  The  con- 
dition is  the  same  in  furuncle  and  carbuncle. 

Acute  osteomyelitis  is  most  frequently  due  to  the  staphylococcus. 
This  is  an  infection  of  the  marrow  of  the  long  bones  often  combined 
with  infection  of  the  periosteum.  Necrosis,  purulent  exudation 
and  softening  is  produced  in  the  marrow  and  the  necrosis  is  ex- 
tended, particularly  when  the  infection  involves  the  periosteum, 
by  closure  of  the  nutrient  vessels  of  the  bone.  Large  areas  of 
necrotic  bone,  sequestra,  are  formed  which  become  gradually  en- 
closed by  a  formation  of  new  bone  called  inwlucrum.  The  or- 
ganisms may  persist  for  months  or  years  in  the  necrotic  tissue  and 
from  this  source  extensions  of  the  infection  take  place  from  time 
to  time.  The  primary  infection  of  the  bone  takes  place  from  the 
blood  and  may  be  secondary  to  some  acute  disease  or  there  may 
be  no  ascertainable  focus  of  primary  infection.  The  process  is 


STAPHYLOCOCCUS  AUREUS  213 

much  the  same  as  in  a  furuncle,  the  difference  being  due  to  the 
nature  of  the  tissue  affected. 

Acute  meningitis,  produced  by  the  staphylococcus  and  resulting 
in  a  fibrino-purulent  exudation  in  the  pia-arachnoid,  is  almost 
always  secondary  to  some  localized  infection  in  the  brain  or  in  the 
adjoining  tissue. 

Acute  peritonitis,  pleuritis  and  pericarditis  may  be  produced, 
usually,  by  extension  of  infection  from  an  adjoining  focus.  The 
exudation  in  the  beginning  is  fibrino-purulent  and  the  longer  the 
process  lasts  the  more  purulent  does  the  exudation  become. 

Acute  endocarditis  is  frequently  caused  by  the  staphylococcus 
and  the  disease  tends  to  assume  the  ulcerative  form  with  de- 
struction of  valves,  and  extension  into  the  myocardium. 

Infection  of  the  blood  may  take  place  from  any  primary  lesions, 
resulting  in  numerous  metastatic  abscesses  in  various  parts  of  the 
body.  In  these  cases  the  metastases  are  often  the  result  of  emboli 
coming  from  infected  thrombi.  These  small  emboli  carry  the 
organisms  and  the  associated  toxic  substances,  and  to  the  effect 
of  these  is  added  the  vascular  occlusion  and  necrosis  of  tissue 
resulting  from  this. 

Degenerative  lesions  in  the  internal  organs  are  common  in  fatal 
cases  of  infection  produced  by  this  organism.  Amyloid  degenera- 
tion often  follows  chronic  osteomyelitis. 

A  CASE  or  LOCAL  AND  GENERAL  INFECTION  WITH  THE 
STAPHYLOCOCCUS  AUREUS 

Anatomical  Diagnoses.  Staphylococcus  aureus  septicaemia;  Sub- 
cutaneous abscesses;  Multiple  abscesses  in  lungs  and  kidneys; 
Congestion  of  lungs;  Slight  acute  swelling  of  spleen;  Acute 
fibrinous  pleuritis;  Chronic  adhesive  pleuritis;  Chronic  mitral 
endocarditis;  Infarction  of  lung;  Healed  tuberculosis  of  mesen- 
teric  lymph  node. 

Male,  white,  age  ten  years.  He  complained  on  October  2yth  of  pain 
in  both  legs  below  the  knees.  Up  to  this  time  he  had  been  perfectly 
well.  Following  the  pain  in  the  knees,  fever  and  some  rigidity  of  the 
muscles  of  the  neck  developed  and  diagnosis  of  cerebrospinal  meningitis 
was  made.  On  examination  when  admitted  to  hospital  November  3rd, 
there  was  no  evidence  of  meningitis  save  the  rigidity  of  the  neck  muscles. 
On  both  legs  below  knees  there  were  tender  blue  discolorations.  Tern- 


214 


PATHOLOGY 


perature  103.    Delirious.    Died  without  developing  further  signs  a  few 
hours  after  entering  hospital. 

Autopsy,  November  4th,  twelve  hours  post  mortem.  Body  that  of  a 
well-developed  and  fairly  well-nourished  boy.  Rigor  mortis  present. 
Marked  lividity  over  dependent  portions  of  body  and  sides  of  neck. 
There  is  purple  discoloration  over  the  anterior  surfaces  of  both  legs, 
especially  marked  on  the  right  side  just  below  the  inner  side  of  the  knee 
joint.  There  is  a  similar  area  on  the  left  side  of  the  lower  jaw.  There 
are  no  petechise.  On  incising  the  areas  of  discoloration  on  the  legs  there 
are  foci  of  pus  in  the  subcutaneous  tissues  and  considerable  turbid  serum. 
This  condition  is  more  marked  on  the  right  leg.  The  knee  joints  and 
bones  of  the  legs  are  normal. 

Subcutaneous  fat  over  body  in  fair  amounts.  Muscles  well  developed. 
The  peritoneum  smooth,  free  from  adhesions.  There  is  a  firm,  rather 
nodular  lymph  node,  2  cm.  in  diameter,  near  the  root  of  the  mesentery 
and  nearest  to  the  duodenum.  On  section  the  contents  are  dry,  gritty 
and  caseous  with  a  distinct  peripheral  capsule.  The  other  mesenteric 
lymph  nodes  are  normal. 

Pleural  cavities.  A  few  old,  firm  adhesions  over  the  right  upper  lobe, 
and  a  fibrinous  exudate  over  the  lower  and  basal  portions  of  the  right 
lower  lobe.  This  is  easily  stripped  from  the  surface  and  is  of  a  yellow 
granular  appearance.  On  the  left  side  the  lobes  are  adherent  to  each 
other  by  thin  fibrous  adhesions. 

Pericardium  and  cavity  normal. 

Heart,  weight,  130  grams.  Epicardium  normal.  There  is  little  sub- 
epicardial  fat.  The  myocardium  is  pale,  of  a  light  chocolate-brown 
tinge  especially  near  the  papillary  muscles.  Consistency  normal. 
There  is  slight  thickening  along  the  free  edge  of  the  anterior  curtain  of 
the  mitral  valve  close  to  the  attachment  of  the  chordae  tendinese.  There 
is  also  a  small  firmly  attached  wart-like  vegetation  on  this  valve.  The 
other  valves  of  the  heart  are  normal. 

Lungs.  The  lower  lobe  of  right  lung  is  of  a  dark  red  color  in  dependent 
portions  and  has  scattered  over  its  surface  a  few  discrete  round  areas 
from  2  to  5  mm.  in  diameter.  On  palpation  these  are  firm  and  on  section 
there  is  an  area  of  purulent  softening  in  the  center.  Others  contain  in 
the  centre  a  small  amount  of  pus  with  intense  congestion  and  haemorrhage 
in  the  periphery.  The  intervening  lung  tissue  is  hyperaemic.  A  few 
small  miliary  abscesses  in  the  middle  and  upper  lobe.  Left  lung  contains 
a  few  miliary  abscesses.  On  the  posterior  surface  of  the  lower  lobe  there 
is  an  area  approximately  5  by  4  cm.,  which  is  firm,  deep  dark  red  in  color 
and  over  which  the  pleural  surface  has  lost  its  luster.  On  section  the 
area  is  solid  and  extends  5  cm.  into  the  lung  tissue  and  is  sharply  cir- 
cumscribed. The  bronchi  contain  thick  viscid  blood-stained  mucus. 


STAPHYLOCOCCUS  AUREUS  215 

Spleen,  weight,  95  grams.  Capsule  is  smooth.  On  section  soft, 
follicles  distinct.  Pulp  easily  separated,  color  dark  red. 

Pancreas  normal. 

Stomach  and  intestines  normal. 

Liver,  weight,  1010  grams.  Capsule  smooth,  color  dark  chocolate 
brown.  Lobular  markings  distinct,  consistency  normal.  A  general 
fine  yellow  mottling  throughout. 

Kidneys,  weight,  195  grams.  Of  equal  size.  Cortex  slightly  swollen. 
Capsule  strips  readily  leaving  a  smooth  pale  surface  on  which  the  stellate 
veins  are  prominent.  On  section  a  few  scattered  miliary  abscesses  are 
seen  varying  in  size  from  i  to  3  mm.,  generally  situated  in  the  cortex  and 
circular  in  outline. 

Adrenals,  genitalia,  aorta  and  organs  of  neck  are  normal. 

Brain,  weight,  1420  grams.  Calvarium  and  meninges  normal.  Sur- 
face and  sections  of  brain  are  all  normal. 

Middle  ears  and  mastoids  normal. 

Cultures  from  blood  and  from  abscesses  all  show  pure  and  abundant 
growth  of  staphylococcus  aureus. 

REMARKS.  The  case  is  that  of  an  acute  infection  with  the 
staphylococcus  aureus,  the  source  of  infection  being  not  ascer- 
tained. This  is  not  uncommon,  a  slight  lesion  on  the  surface  may 
be  overlooked,  or  may  have  healed  and  no  recognizable  trace  remain 
and  the  organism,  after  existing  for  a  time  in  some  internal  focus, 
may  have  suddenly  invaded  the  blood  and  produced  the  metastases. 
In  these  conditions  the  organism  is  usually  one  of  great  virulence. 
Both  the  clinical  and  autopsy  findings  show  that  the  subcutaneous 
abscesses  below  knees  were  the  oldest  of  the  metastatic  abscesses. 
The  bi-symmetry  of  these  is  probably  accidental.  The  purple  color 
of  the  skin  over  them,  due  to  intense  congestion  with  haemorrhage, 
led  to  the  thought  of  purpura  on  the  first  inspection  of  the  body 
and  the  note  "no  ecchymoses"  indicates  the  thought  and  the 
exclusion.  The  abscesses  in  the  lungs  and  kidneys  are  due  to 
haemotogenous  infection.  Note  the  varying  size  of  those  in  lung 
which  indicates  differences  in  time  of  infection.  In  the  lung  there 
is  also  an  area  of -congestion,  haemorrhage  and  necrosis  described 
as  an  infarction.  No  thrombus  as  the  source  of  the  embolus  which 
produced  the  infarction  was  seen,  but  there  was  almost  surely 
thrombosis  in  some  of  the  small  veins  adjoining  the  subcutaneous 
abscesses  which  gave  origin  to  the  emboli.  There  is  a  slight  acute 


2x6  PATHOLOGY 

swelling  of  the  spleen  due  to  acute  congestion.  Meningitis  was 
suggested  clinically  from  the  delirium  and  the  rigidity  of  neck 
muscles.  These  symptoms  were  due  to  the  effect  on  the  brain  of 
the  toxic  condition  of  the  blood. 

There  had  been  two,  and  possibly  more,  previous  infections. 
The  evidence  in  the  mitral  valve  of  a  previous  acute  endocarditis 
which  had  healed  leaving  a  valve  slightly  thickened  with  a  small 
mass  of  organized  tissue  upon  it  but  functioning  perfectly.  A  fresh 
staphylococcus  infection  at  this  point  could  easily  have  taken  place. 
The  caseous  and  calcareous  mesenteric  lymph  node  is  evidence  of 
a  previous  infection  with  tubercle  bacilli  from  the  intestinal  canal. 
Without  the  demonstration  of  tubercle  bacilli  either  microscopi- 
cally or  by  animal  inoculation  this  cannot  be  regarded  as  certain, 
but  the  relation  of  a  caseous  and  partly  calcified  lymph  node  to 
tuberculosis  is  almost  sure.  This  old  tuberculous  infection  took 
place  from  the  alimentary  canal.  The  old  pleuritic  adhesions  may 
have  been  due  to  infection  of  the  pleura  which  occurred  at  the 
tune  of  the  endocarditis  on  to  an  independent  infection. 


STREPTOCOCCUS  PYOGENES 

Streptococci  divide  in  one  dimension  of  space,  the  individuals 
adhering  and  forming  chains.  There  is  considerable  variation  in 
the  length  of  the  chains.  The  streptococci  form  on  solid  media 
minute  dew-like  colonies;  in  bouillon,  the  growth  is  more  rapid 
and  they  form  long  tortuous  chains  which  have  a  tendency  to 
adhere,  forming  flakes  in  the  medium.  Gelatine  is  not  liquefied. 
In  cultures  most  streptococci  produce  a  haemolysin,  but  it  has  not 
been  possible  to  explain  at  all  the  pathogenic  action  of  the  organisms 
by  such  toxic  products  as  can  be  isolated  from  them.  The  optimum 
culture  temperature  is  37^  degrees;  at  room  temperature  the  growth 
is  feeble,  the  cultures  lose  their  virulence  and  easily  die. 

In  no  pathogenic  organisms  is  there  so  much  variation  in  viru- 
lence. Some  have  no  virulence,  in  others  the  virulence  is  feeble 
and  in  others  the  virulence  is  so  great  that  the  body  seems  utterly 
devoid  of  resistance  and  the  organisms  produce  but  little  leucocytic 
reaction.  Of  the  laboratory  animals  white  mice  and  rabbits  are 
the  most  susceptible  to  infection. 

The  streptococci  may  produce  typical  suppuration  and  abscess 
in  the  tissue.  As  a  general  rule  the  foci  of  infection  are  less  circum- 
scribed than  those  produced  by  the  staphylococci,  there  is  more 
surrounding  oedema  and  a  greater  tendency  for  the  infection  to 
extend  by  the  lymphatics.  Secondary  infection  is  more  frequently 
produced  by  the  streptococci  than  by  other  organisms. 

Primary  and  especially  secondary  infections  frequently  take 
place  from  the  mouth.  Streptococci  are  so  commonly  found  in 
the  mouth  that  they  can  almost  be  considered  normal  inhabitants, 
and  in  case  the  normal  resistance  of  the  tissues  is  diminished, 
infections  of  the  lungs  by  way  of  the  bronchi  or  of  the  middle  ears 
by  extension  along  the  Eustachian  tubes  easily  results.  So  com- 
mon is  the  streptococcus  infection  of  the  middle  ear  in  children 
under  one  year  of  age  that  it  is  a  frequent  finding  at  autopsies, 
and  the  same  may  be  said  of  streptococcus  broncho-pneumonia. 
Of  the  primary  infections  in  the  mouth  the  most  frequent  is  acute 
tonsilitis,  the  entry  of  the  organisms  taking  place  from  the  crypts. 

217 


2i8  PATHOLOGY 

The  organism  is  also  a  frequent  cause  of  acute  endocarditis  and 
inflammations  of  the  serous  membranes.  The  exudate  in  the  latter 
is  rarely  abundant  and  contains  but  little  fibrin,  and  the  vascular 
reactions  are  but  little  marked.  It  also  is  the  organism  most 
frequently  concerned  in  the  post  partum  infections  of  the  uterus; 
the  infection  takes  place  usually  at  the  placental  site  and  a  diffuse 
suppurative  inflammation  with  extensive  necrosis  is  produced. 
The  infection  may  extend  to  the  parametrium  by  way  of  the  lym- 
phatics and  thence  into  the  peritoneum.  The  blood  usually  is 
infected,  but  metastatic  abscesses  do  not  so  frequently  result  as  in 
staphylococcus  infection.  Notwithstanding  the  fact  that  there  is 
but  little  evidence  of  toxin  production  by  the  streptococci  in  cul- 
tures, there  is  marked  constitutional  disturbance  in  the  infections 
and  the  internal  organs  show  evidences  of  the  action  of  toxins. 
Focal  necrosis  of  the  liver  and  acute  glomerular  nephropathy  is 
frequent. 

The  streptococci  are  the  cause  of  an  acute  inflammation  of  the 
skin  which  is  called  erysipelas.  The  infection  is  in  the  corium, 
there  is  intense  redness  and  swelling  of  the  skin  which  gradually 
extends  over  the  surface  and  which  is  most  marked  at  the  line  of 
extension.  The  exudation  is  serous  or  sero-purulent  and  may 
extend  through  the  epithelium,  lifting  up  the  horny  layer  in  the 
form  of  blebs.  The  streptococci  are  found  in  the  lymphatics  of 
the  corium  and  chiefly  at  the  advancing  edge.  The  subcutaneous 
tissue  may  become  infected,  a  diffuse  phlegmonous  inflammation 
with  much  necrosis  resulting.  No  demonstrable  specificity  is 
attached  to  the  organism  which  produces  erysipelas;  infection  from 
this  source  is  not  characterized  by  any  peculiar  features. 

A  CASE  OF  STREPTOCOCCUS  INFECTION  OF  THE  UTERUS 
PROBABLY  FOLLOWING  ABORTION 

Anatomical  Diagnoses.  Acute  septic  endometritis  of  puerpural 
uterus;  Acute  purulent  metritis;  Acute  fibrinous  pleuritis; 
Empyema  of  left  side;  Bilateral  haematogenous  abscesses  of  lungs; 
Acute  splenic  tumor;  Acute  glomerular  nephropathy;  Lacera- 
tion and  erosion  of  external  os  uteri. 

Female,  white,  age  thirty-six  years.    The  patient  came  into  the  hospi- 
tal in  evening  in  semi-moribund  condition  with  signs  of  pleural  effusion 


STREPTOCOCCUS  PYOGENES  219 

on  left  side.  Died  the  next  morning  without  being  at  any  time  fully 
conscious. 

Body  that  of  a  well  developed  and  well  nourished  female.  Rigor 
mortis  in  extremities.  Surface  normal.  Both  breasts  enlarged.  On 
section  of  mammary  glands  a  whitish  opaque  material  exudes  and  on 
pressure  the  same  can  be  expressed  from  the  nipples.  Abdominal  fat 
abundant,  pale,  yellow.  Muscles  red. 

Peritoneum.  The  large  intestine  greatly  distended  with  gas.  Mesen- 
teric  lymph  nodes  not  enlarged.  The  spleen  shows  a  few  soft  fibrinous 
adhesions  on  the  surface. 

The  left  pleural  cavity  contains  600  c.c.  of  reddish-grey  turbid  fluid 
containing  fibrin.  The  lung  is  collapsed,  its  pleural  surface  covered  with 
a  fairly  firm  fibrino-purulent  exudation  over  an  intensely  congested  lung 
surface.  Over  the  pleura  of  the  right  lung  there  is  a  patch  of  exudate 
on  the  posterior  portion  of  the  lower  lobe  similar  to  that  over  the  left 
lung.  The  pericardium  and  heart  normal. 

Lungs.  The  left  lung  small,  compressed.  The  lower  lobe  on  section 
is  granular  and  nodular.  In  one  of  the  larger  foci  of  consolidation  there 
is  a  cavity  i  cm.  in  diameter  filled  with  thin  purulent  material.  Similar 
nodules  are  found  in  the  lower  lobe  of  the  right  lung. 

Liver  of  ordinary  size,  the  consistency  normal. 

Spleen  large,  its  capsule  tense,  showing  a  few  soft  fibrinous  tags.  On 
section,  pulp  bulges  at  edges,  is  soft  and  grey-red  in  color.  Follicles 
large. 

Both  kidneys  are  alike.  The  capsule  strips  easily,  leaving  a  smooth, 
pink-gray  surface  on  which  the  stellate  veins  are  very  prominent.  On 
section  the  cortex  is  pale,  increased  in  size,  bulges  slightly  at  cut  edges. 
The  markings  are  obscure.  The  glomeruli  are  visible  as  pale  sand-like 
glistening  bodies  the  size  of  pin  points.  The  vessels  of  pyramids  in- 
jected. 

Adrenals,  pancreas,  gastro-intestinal  tract  normal. 

Genito-urinary  tract.  The  uterus  is  enlarged,  the  parametrium  is 
smooth  and  shiny  except  on  left  side  where  the  ovary  is  adherent.  The 
external  os  measures  2  cm.  transversely.  Its  edges  are  ragged  and  torn, 
the  lips  smooth,  everted,  showing  dark  brownish  erosions  on  the  mucosa. 
The  wall  of  the  uterus  is  thickened,  averaging  3  cm.  The  sinuses  are 
easily  seen.  The  cavity  of  the  uterus  is  regularly  enlarged,  the  endome- 
trium  of  a  dark  brown  color.  On  the  anterior  surface  there  is  an  irregular 
ragged  necrotic  mass.  On  section  of  the  uterus  beneath  this  the  wall  is 
distinctly  softened  and  pus  can  be  squeezed  from  the  cut  surface.  In 
the  region  of  the  cervix  there  is  a  cavity  in  the  wall  i  cm.  in  diameter 
filled  with  purulent  material,  and  smaller  cavities  are  throughout  the 


PATHOLOGY 

lower  part  of  the  uterus.  In  the  left  ovary  which  is  adherent  to  the 
uterus  there  is  a  large  corpus  luteum.  Smears  from  uterus  and  pleural 
cavity  showed  abundant  streptococci  in  short  chains  together  with  con- 
taminating organisms  seemingly  of  colon  group.  Cultures  gave  abundant 
growth  of  streptococci  and  colon  bacilli. 

Microscopic  examination.  Sections  of  lung  showed  numerous  foci 
of  purulent  infiltration  with  masses  of  streptococci.  The  exudation  on 
the  pleura  showed  streptococci.  The  sections  of  kidney  show  character- 
istic lesions  in  the  glomeruli  consisting  in  occlusions  of  capillaries  by 
cells  of  endothelial  type  with  well  marked  degeneration  of  epithelium. 
The  muscle  fibres  of  the  uterus  large.  Corresponding  to  the  ulcerated 
area  on  the  anterior  surface  of  the  endometrium  there  are  necrotic 
masses  with  fibrin  and  blood.  In  the  submucosa  and  muscularis  are 
large  areas  infiltrated  with  polynuclear  leucocytes.  In  the  small  vessels 
of  the  uterus  in  the  vicinity  of  these  there  are  fresh  thrombi.  Strepto- 
cocci in  large  numbers  are  found  in  association  with  the  lesions. 

REMARKS.  The  case  is  one  of  pregnancy  with  delivery  at  about 
the  eighth  month.  The  case  was  regarded  as  one  of  induced 
abortion.  Streptococcus  infection  of  the  uterus  followed,  the 
infection  probably  taking  place  at  the  placental  site.  An  extension 
of  the  infection  from  the  body  of  the  uterus  by  means  of  the  lym- 
phatics to  the  parametrium  followed,  resulting  in  the  circumscribed 
fibrinous  inflammation  involving  the  ovary  in  the  fibrinous  adhe- 
sions. There  is  also  a  focal  infection  of  the  peritoneum  shown  by 
the  fresh  fibrin  on  the  spleen;  infection  of  the  blood  took  place  pro- 
bably through  the  uterine  sinuses  and  following  this  the  abscesses  in 
the  lung,  the  fresh  fibrinous  pleurisy  and  the  empyema.  All  these 
lesions  are  due  to  the  direct  action  of  the  organisms  on  the  tissues. 
The  acute  glomerular  nephropathy  is  due  to  the  action  of  toxins. 

A  CASE  OF  STREPTOCOCCUS  INFECTION  OF  THE  MIDDLE  EAR  INVOLVING 
MASTOID  WITH  EXTENSION  TO  BRAIN 

Anatomical  Diagnoses.  Acute  otitis  media;  Necrosis  and  per- 
foration of  roof  of  middle  ear;  Acute  purulent  meningitis;  Acute 
glomerular  nephropathy;  General  parenchymatous  degeneration; 
Focal  necrosis  of  liver;  Old  healed  tuberculosis  of  lungs;  Strep- 
tococcus infection. 

Female,  white,  twenty-seven  years  old.  Body  of  medium  size,  poorly 
nourished,  skin  loose  and  dry.  Pupils  unequal.  Immediately  behind 


STREPTOCOCCUS  PYOGENES  221 

left  ear  extending  obliquely  downwards  and  backwards  from  the  mastoid 
process  is  an  incision  6  cm.  long  with  a  large  funnel-shaped  excavation 
into  the  mastoid  process.  The  wound  is  bathed  in  blood-tinged  pus. 
With  a  probe,  direct  communication  is  found  between  the  wound  and 
the  intracranial  cavity.  Subcutaneous  fat  is  small  in  amount,  muscle 
pale. 

Peritoneum  normal. 

Pleurae:  Numerous  dense  adhesions  at  both  apices  posteriorly.  Epi- 
cardium  normal. 

Heart  205  grams.    Endocardium  smooth.    Coronaries  normal. 

Lungs.  At  both  apices  extending  into  the  lung  substance  are  numerous 
larger  and  smaller  firm  areas  with  puckering  of  the  overlying  pleural 
surface.  On  section  the  larger  areas  average  3  to  4  mm.  Their  centres 
are  yellowish,  dense  and  sometimes  calcareous.  Surrounding  these 
larger  areas  are  a  few  small  hard  miliary  foci.  The  intervening  lung 
substance  is  crepitant.  Elsewhere  the  lungs  are  normal. 

Liver,  weight  1600  grams.  The  normal  lobulation  evident  on  surface 
and  on  section.  Consistency  fairly  firm. 

Spleen  190  grams.  Soft,  cut  surface  dark  red.  Trabeculae  and  mal- 
pighian  bodies  visible.  The  pulp  is  soft,  the  capsule  smooth,  tense,  but 
not  thickened.  Pancreas  normal. 

Kidneys,  weight  together  325  grams.  Surface  smooth,  capsule  easily 
stripped.  On  section,  cortex  smooth,  somewhat  enlarged  and  bulges 
above  pyramids.  The  glomerulae  are  visible,  appearing  as  pale  points. 
Pelvis  and  ureters  normal.  Adrenals  normal. 

Gastro-intestinal  tract  normal.  Genitalia  normal.  The  aorta  for  the 
most  part  smooth,  but  contains  a  few  slightly  elevated  yellowish  areas 
extending  in  the  long  axis. 

Head  and  brain.  Scalp  strips  readily  from  calvarium.  On  the  left 
side  of  the  skull  practically  the  entire  mastoid  process  has  been  removed. 
The  dura  is  slightly  injected.  The  pia  arachnoid  over  left  cerebral 
hemispheres  shows  numerous  scattered  areas  of  purulent  infiltration, 
the  areas  of  small  size  from  £  to  i  cm.  and  situated  about  the  vessels. 
The  cerebral  surface  of  the  tentorium  is  pale,  smooth  and  free  from 
exudation.  Over  the  base  of  the  cerebrum,  particularly  about  pons  and 
medulla,  there  is  an  abundant  fibrino-puiulent  exudation.  The  cere- 
bellar  surface  of  the  tentorium  is  bathed  in  pus  and  the  entire  surface 
of  the  cerebellum  is  thickly  covered  with  fibrino-purulent  exudation. 
At  the  base  of  the  left  temporal  lobe  there  is  a  slightly  softened  area  of 
cortex  measuring  i|  cm.  and  infiltrated  with  blood.  In  the  lateral  ven- 
tricles there  is  a  considerable  amount  of  turbid  opalescent  fluid .  Sections 
of  brain  show  no  lesions  elsewhere.  There  is  an  opening  0.2  cm.  in  diameter 


222  PATHOLOGY 

into  the  left  middle  ear  through  the  tegmen  tympani.  On  the  edge  of  this 
opening  the  bone  is  necrotic  and  the  opening  corresponds  to  the  area 
of  softening  hi  the  temporal  lobe.  The  left  middle  ear  is  filled  with  thick 
pus,  the  surface  covered  with  granulation  tissue.  The  drum  is  absent. 
The  jugular  vein  is  free  from  thrombi. 

Microscopic  examination.  Lungs.  Section  through  two  of  the 
caseous  nodules  show  in  the  centre  caseous  necrotic  masses  surrounded 
by  dense  hyalin  connective  tissue  with  numerous  lymphoid  and  plasma 
cells  at  the  outer  edge  of  this.  Thick  bands  of  the  connective  tissue 
radiate  from  the  capsule  into  the  surrounding  lung  tissue  and  the  closely 
adjacent  alveoli  are  collapsed.  The  small  miliary  foci  are  composed  of 
nodules  of  connective  tissue.  A  few  giant  cells  on  the  edges  of  the  case- 
ous mass  are  seen.  In  the  liver  the  sinusoids  are  distended  with  blood 
and  contain  numerous  polynuclear  leucocytes  and  endothelial  cells.  In 
numerous  places  about  the  central  vein  there  are  foci  of  necrosis.  These 
are  not  everywhere  present. 

The  spleen  is  deeply  injected  with  numerous  foci  of  haemorrhage  in 
the  pulp.  There  are  numerous  polynuclear  leucocytes  throughout  the 
pulp  and  mitotic  figures  occasionally  are  found  in  the  endothelial  cells 
of  the  sinuses. 

The  kidneys.  There  is  very  marked  acute  parenchymatous  degenera- 
tion of  the  epithelium  of  the  convoluted  tubules.  The  cells  are  swollen 
and  in  the  proximal  tubules  the  swollen  cells  contain  round  hyalin 
masses.  Similar  masses  are  also  found  within  the  lumen.  The  glomeruli 
are  large,  swollen,  the  tufts  entirely  rilling  the  capsule.  There  is  a  general 
increase  hi  the  cells,  the  capillaries  contain  numerous  large  cells  of  endo- 
thelial character  and  polynuclear  leucocytes.  The  covering  epithelium 
is  in  places  swollen.  In  some  of  the  capillaries  of  the  glomeruli  there 
are  well  defined  fibrinous  thrombi.  Throughout  the  cortex  there  is 
considerable  infiltration  with  polynuclear  leucocytes,  this  particularly 
about  the  glomeruli. 

The  pia  arachnoid  covering  the  cerebrum  and  cerebellum  is  densely 
infiltrated  with  fibrino-purulent  exudation.  The  vessels  are  dilated  and 
migrating  leucocytes  are  seen  in  their  walls.  In  the  exudation  there  are 
numerous  large  mononuclear  cells,  many  of  which  contain  polynuclear 
leucocytes.  Streptococci  are  found  in  the  exudate  and  within  the  cells. 
Smears  and  cultures  from  the  exudation  in  the  meninges  gave  strepto- 
cocci. In  the  meninges  the  cultures  were  contaminated  with  other 
organisms.  Cultures  of  the  heart's  blood  showed  a  pure  culture  of 
streptococci. 


STREPTOCOCCUS  PYOGENES  223 

REMARKS.  The  case  is  one  of  otitis  media,  due  to  streptococcus 
infection.  The  infection  from  the  middle  ear  has  extended  into 
the  mastoid  cells.  Necrosis  of  the  bone  has  been  produced  and 
the  infection  has  extended  to  the  meninges  and  brain.  Of  the 
lesions  in  the  organs,  the  most  interesting  and  important  is  the 
acute  glomerulo  nephropathy.  This  is  not  an  infrequent  accom- 
paniment of  streptococcus  infection.  The  diffuse  character  of 
the  lesions  in  the  kidney  indicates  that  they  are  produced  not  by 
the  bacteria  acting  directly  on  the  tissue  but  by  toxic  substances. 
There  is  also  in  the  case  a  slight  degree  of  central  necrosis  in  the 
liver. 


DIPLOCOCCUS   PNEUMONLE   (PNEUMOCOCCUS.    DIPLO- 

COCCUS  LANCEOLATUS) 

This  is  a  coccus  which  in  the  body  or  in  cultures  occurs  in  pairs. 
The  organism  is  elongated  or  lancet  shaped,  in  pairs,  rounded  on 
the  contiguous  sides,  the  opposite  ends  bluntly  pointed.  The  most 
characteristic  morphological  peculiarity  is  the  capsule  formation 
around  the  pairs  of  the  organism.  This  always  is  found  around 
organisms  when  growing  in  the  blood  and  tissues  and  may  be 
produced  in  cultures  containing  blood  or  animal  fluids.  The 
organism  stains  with  the  Gram  stain.  Growth  in  culture  is  not 
vigorous,  appearing  on  solid  media  as  minute  dew-like  colonies 
somewhat  resembling  streptococci  but  more  transparent.  Cultural 
conditions  show  that  it  is  an  exclusive  parasite.  No  characteristic 
soluble  toxin  has  been  obtained.  The  toxic  properties  seem  to  be 
due  to  an  endotoxine  closely  bound  with  the  protoplasmic  substance. 
Injection  into  animals  gives  varying  results,  mice  and  rabbits 
being  the  most  susceptible.  The  virulence  of  the  organisms  de- 
rived from  different  sources  varies  greatly  and  the  virulence  is 
quickly  lost  in  cultures. 

In  animals  local  lesions  with  abundant  formation  of  fibrin  may 
be  produced  or  the  organism  enters  into  the  blood  and  produces 
a  fatal  septicaemia.  Not  infrequently  virulent  cultures  produce 
in  rabbits  hyalin  thrombi  in  the  glomeruli  of  the  kidneys  due  to 
agglutination  and  fusion  of  the  red  blood  corpuscles. 

In  man  the  organism  is  a  frequent  source  of  both  primary  and 
secondary  infections.  It  is  a  frequent  cause  of  otitis  media  and 
inflammation  of  the  accessory  sinuses  of  the  nose,  the  infection 
taking  place  from  the  mucous  surfaces  where  the  organisms  fre- 
quently are  found  in  symbiosis.  In  addition  acute  endocarditis 
and  acute  inflammation  of  the  serous  surfaces  and  of  the  meninges 
may  be  due  to  primary  haematogenous  infection,  the  organism 
probably  entering  the  blood  from  some  concealed  focus;  or  these 
infections  can  be  secondary  to  some  other  focus  of  infection,  the 
extension  being  by  continuity  or  by  the  blood.  Infection  of  the 
subcutaneous  tissues,  or  infection  of  the  parenchyma  of  organs 

224 


DIPLOCOCCUS  PNEUMONLE  225 

occurs  more  rarely.  On  serous  surfaces  the  exudate  usually  con- 
tains large  amounts  of  fibrin.  The  organism  has  been  described 
as  a  cause  of  enteritis,  and  infection  of  the  Fallopian  tube  may  also 
occur.  In  very  young  infants  infection  of  the  blood  very  similar  in 
character  to  the  septicaemia  produced  in  mice  may  take  place. 
The  focus  of  infection  in  these  cases  may  be  concealed  and  the 
blood  contains  great  numbers  of  the  organisms  with  well-marked 
capsules. 

As  the  name  of  the  organism  implies,  the  lung  is  the  most  com- 
mon site  of  infection  in  man.  Acute  croupous  or  lobar  pneumonia 
in  man  is  most  generally  associated  with  this  organism.  This  is 
an  acute  inflammation  of  the  lung  which  affects  simultaneously 
lobes  or  large  areas,  and  is  characterized  by  an  abundant  exudation 
of  fibrin,  red  corpuscles  and  leucocytes  into  the  air  spaces.  Three 
well-defined  stages  of  the  lesions  are  distinguished.  In  the  stage 
of  engorgement  the  tissue  is  deep  red,  firmer  than  normal  to  the 
touch,  but  not  solid  and  on  section  blood  and  fluid  exudes.  The 
tissue  floats  in  water,  but  the  submergence  is  greater  than  normal. 
Microscopically,  there  is  intense  congestion  of  the  capillaries,  the 
loops  of  which  extend  into  the  air  spaces,  and  some  serous  exudation. 
This  passes  into  the  stage  of  red  hepatization  in  which  the  tissue  is 
solid,  sections  sink  in  water,  and  the  redness  is  not  so  pronounced 
as  in  the  previous  stage.  The  cut  surface  is  finely  granular  due  to 
the  projection  of  fibrin  plugs  from  the  alveoli  and  on  scraping  with 
a  knife  these  are  removed  as  granules.  The  tissue  is  seemingly 
more  friable,  the  finger  can  be  pushed  into  it,  and  sections  break 
on  bending.  This  is  due  to  the  solidification  of  the  tissue  prevent- 
ing the  distribution  of  the  applied  force  over  a  larger  area.  Micro- 
scopically at  this  stage  the  congestion  is  no  longer  so  marked  and 
the  alveoli  are  filled  with  exudate  which  consists  of  red  corpuscles, 
leucocytes  and  fibrin.  The  relative  amounts  of  the  constituents 
of  the  exudation  varies  in  different  cases.  There  is  usually  some 
proliferation  and  desquamation  of  the  alveolar  epithelium.  The 
third  stage  is  that  of  gray  hepatization.  In  this  the  red  color  gives 
place  to  a  gray  or  grayish  red.  The  solidification  remains  but  the 
cut  surface  is  smoother,  more  moist,  and  a  turbid  granular  fluid 
is  removed  by  scraping.  Microscopic  examination  at  this  period 
shows  the  leucocytes  relatively  more  abundant  than  in  the  early 
stage.  The  lymphatics  both  the  subpleural  and  the  central  are 


226  PATHOLOGY 

distended  and  filled  with  cells  and  fluid.  A  fourth  stage  resolution 
follows  in  favorable  cases.  In  resolution  the  exudation  undergoes 
autolysis  by  the  action  of  proteolytic  enzymes  and  is  chiefly  ab- 
sorbed, although  some  passes  out  by  the  bronchi. 

The  entire  lung  may  be  involved  and  show  the  same  stage  of 
the  disease,  or  lobes  of  both  lungs  may  be  affected  and  different 
stages  may  be  found  in  different  areas.  The  pleura  always  is 
involved  and  the  exudate  has  the  same  character  as  in  the  alveoli; 
extension  to  the  pericardium  also  is  not  infrequent.  The  internal 
organs  do  not  present  much  evidence  of  toxic  action,  the  spleen  is 
but  little  enlarged  and  the  parenchymatous  degeneration  of  liver 
and  kidneys  is  not  marked. 

Pneumococci  are  found  in  variable  numbers  and  are  both  within 
the  leucocytes  and  free.  They  are  always  more  abundant  in 
the  earlier  stages.  In  rare  cases  the  condition  of  carnification 
of  the  lung,  or  chronic  pneumonia,  or  organizing  pneumonia  super- 
venes on  the  acute.  In  this  condition  autolysis  and  absorption  of 
the  exudate  does  not  take  place  and  it  becomes  organized  by  the 
in  growth  of  connective  tissue  from  the  walls  of  the  alveoli  and  from 
the  peribronchial  connective  tissue.  The  exudation  in  the  inter- 
lobular  septa  undergoes  the  same  fate.  The  lung  in  color  and  con- 
sistency approaches  that  of  muscle.  Microscopically,  both  alveoli 
and  small  bronchi  are  filled  with  vascular  granulation  tissue  which 
later  gives  place  to  connective  tissue.  The  process  of  organization 
is  accompanied  by  thickening  of  the  alveolar  walls  and  abundant 
formation  of  elastic  tissue.  The  process  can  involve  entire  lobes 
of  the  lung  or  appear  in  small  foci.  The  lung  so  altered  appears 
to  be  much  less  resistant  to  infection  than  the  normal  lung  and 
both  abscess  and  gangrene  are  not  uncommon  accompanying 
conditions. 

In  the  acute  infectious  diseases  of  children  focal  infections  of  the 
lung  with  the  diplococcus  pneumonias,  the  organisms  entering  and 
extending  by  the  bronchi  (broncho-pneumonia)  and  producing  small 
areas  of  solidification,  are  common.  It  is  certainly  very  remarkable 
that  the  same  organism  should  produce  in  the  one  case  so  characteris- 
tic a  lesion  as  lobar  pneumonia  and  in  the  other  small  foci  of  infection 
not  differing  from  the  lesions  produced  by  a  number  of  organisms, 
and  that  there  is  so  little  tendency  for  both  types  to  occur  simul- 
taneously. The  peculiar  action  of  the  pneurnococcus  in  producing 


DIPLOCOCCUS  PNEUMONLE  227 

lobar  pneumonia  is  very  similar  to  that  of  the  streptococcus  in 
producing  erysipelas.  Nothing  that  we  know  of  the  organisms  in 
either  case  gives  a  sufficient  explanation. 


A  CASE  OF  PNEUMONIA 

Anatomical  Diagnoses.  Acute  croupous  pneumonia  of  left  lung 
with  beginning  resolution  in  upper  lobe;  Acute  pleuritis  on  left 
side;  Chronic  adhesive  pleuritis  and  peritonitis;  Acute  swelling 
of  spleen;  Acute  otitis  media;  Fatty  degeneration  of  intima  of 
aorta;  Congestion  and  acute  degeneration  of  liver  and  kidneys. 

White,  male,  aged  twenty-two  years.  Entered  hospital  two  days 
before  death.  Five  days  before  entrance  had  a  chill  which  was  followed 
by  continuous  fever.  Has  now  a  slight  cough,  and  complains  of  dys- 
pnoea and  pain  in  left  side  of  chest  on  coughing  and  breathing.  On 
examination  the  face  is  flushed,  the  pulse  100,  temperature  103.5;  ues  on 
left  side.  There  is  dullness  on  percussion  over  the  entire  left  lung  extend- 
ing posteriorly  to  axillary  line,  with  bronchial  breathing.  Whispering 
voice  more  plainly  heard  and  voice  vibrations  transmitted  to  hand  on 
this  side.  A  friction  rub  is  heard  in  the  axillary  region.  A  blood  count 
shows  a  leucocytosis  of  45,000  with  89  per  cent  polynuclears.  On  the 
following  day  temperature  remained  elevated,  the  dullness  and  bronchial 
breathing  increased,  extending  over  the  entire  area  of  lung;  the  cyanosis 
is  also  increased.  Death  at  7  A.M.  the  following  day. 

Body  that  of  a  fairly  well  developed  and  fairly  well  nourished  white 
male.  Slight  rigor  mortis.  No  oedema. 

Subcutaneous  fat  in  fair  amount.    Muscles  red  and  well  developed. 

Peritoneum.  Smooth  and  normal  save  for  adhesions  between  omen- 
turn  and  abdominal  wall  over  a  small  area  in  the  right  iliac  fossa  and 
about  the  gall  bladder.  The  liver  somewhat  depressed.  Diaphragm 
on  left  side  at  sixth  rib,  on  right  at  fifth  interspace. 

Pleural  cavities.  On  the  left  side  the  visceral  and  parietal  pleurae  are 
loosely  united  by  delicate  fibrinous  adhesions.  The  pleural  surfaces 
have  lost  their  lustre  and  in  part  are  covered  with  reticular  masses  of 
fibrin,  in  part  the  surface  is  granular  and  roughened.  The  exudate  is 
easily  removed  from  the  visceral  pleura,  leaving  an  injected  opaque 
surface.  The  parietal  pleura  can  be  stripped  off  in  large  sheets,  which, 
observed  by  transmitted  light,  show  deeply  injected  enlarged  vessels,  in 
the  course  of  which  small  red  areas,  up  to  2  mm.  in  diameter,  are  seen. 
In  the  right  pleural  cavity  the  surfaces  hi  several  places  are  united  by 
fibrous  bands  most  numerous  over  the  lower  lobe. 


228  PATHOLOGY 

Lungs.  The  left  lung  is  greatly  increased  in  size,  weight  1510  grams. 
The  two  lobes  lightly  united  by  fibrinous  adhesions.  Over  the  surface 
there  are  slight  depressions  corresponding  to  the  ribs.  The  entire  lung 
completely  solidified  save  for  a  narrow  area  along  the  anterior  edge  of  the 
upper  lobe.  Portions  cut  from  various  places  sink  in  water.  On  section 
the  upper  lobe  is  pale  grayish-red.  The  cut  surface  is  moist  and  smooth. 
On  scraping  with  knife,  a  thick  viscid  muco-purulent  material  is  obtained, 
and  on  squeezing  the  tissue  a  similar  fluid  can  be  expressed  from  the  cut 
bronchi.  The  color  of  the  section  is  not  homogeneous,  in  places  more 
gray,  in  others  redder.  The  line  of  demarkation  between  the  solidified 
upper  lobe  and  the  air-containing  edge  is  irregular.  The  section  of  the 
lower  lobe  shows  complete  consolidation,  the  cut  surface  redder  than 
that  of  the  upper  lobe  and  more  granular.  On  scraping  this  with  the 
knife,  small  sand-like  granules  of  irregular  size  are  obtained.  Both  lungs 
are  more  friable,  easily  penetrated  by  the  finger  and  on  bending  a  slice 
of  the  tissue  i  cm.  thick,  it  fractures,  leaving  a  rough  granular  surface. 

The  right  lung  is  smaller  than  the  left  and  contains  air  throughout. 
The  posterior  part  of  the  lower  lobe  is  moist. 

Bronchial  lymph  nodes.  These  are  enlarged,  contain  a  small  amount 
of  carbon  pigment,  on  section  are  of  opaque  grayish-red  color  and  are 
softer  than  normal. 

Pericardium.    Normal.    A  slight  increase  in  the  pericardial  fat. 

Heart.  Weight  340  grams.  The  right  side  of  the  heart  is  dilated 
and  contains  a  tough  elastic  clot,  the  upper  surface  of  which  is  pale 
yellowish-white,  the  lower  dark  red.  This  clot  extends  as  a  branching 
mass  into  the  pulmonary  artery.  The  left  heart  contracted,  valves  and 
coronary  arteries  normal.  Gastro-intestinal  tract  normal. 

Spleen.  Weight  320  grams.  Capsule  smooth,  consistence  soft,  on 
section  deep  red,  pulp  easily  pressed  out,  trabeculae  and  malpighian 
bodies  obscure. 

Pancreas.    Normal. 

Liver.  Weight  1800  grams.  Surface  smooth,  somewhat  mottled  and 
on  section  hyperaemic.  Gall  bladder  small,  contains  a  few  cubic  centi- 
meters of  bile. 

Kidneys.  Weight  295  grams.  Capsule  easily  removed.  Surface 
smooth.  On  section  cortical  markings  visible,  cortex  more  opaque, 
pyramids  injected. 

Adrenals  normal. 

Bladder  and  genitalia  normal. 

In  the  aorta  there  are  a  few  small,  not  elevated,  linear  opacities,  which 
are  most  marked  in  abdominal  aorta,  a  few  only  being  in  the  arch. 

Calvarium  and  dura  normal. 


DIPLOCOCCUS  PNEUMONLE  229 

The  longitudinal  sinuses  contain  fluid  blood  and  clots.  Vessels  of 
pia  congested.  Brain  and  cord  normal. 

Marrow  of  femur  is  almost  replaced  by  red  marrow. 

Right  middle  ear  contains  thick  yellow  pus,  drum  membrane  not 
perforated. 

Cover  slips  made  from  the  lower  lobe  of  the  lungs  show  encapsulated 
diplococci  in  large  numbers  both  within  polynuclear  cells  and  free. 
Cultures  from  the  lungs,  the  blood,  the  spleen  and  kidneys  give  abundant 
pure  cultures  of  pneumococci.  From  the  ear  a  mixed  culture  of  pneu- 
mococci  and  staphylococci  is  obtained. 

REMARKS.  The  change  in  resonance,  in  sound  conduction,  and 
the  transmission  of  sound  vibrations  to  the  chest  wall  are  due  to  the 
changing  of  the  lung  from  an  elastic  air  cushion  to  a  solid  body.  The 
increased  number  of  polynuclear  leucocytes  in  the  blood  is  due  to 
their  greatly  increased  formation  in  the  bone  marrow,  the  number 
removed  from  the  blood  in  the  formation  of  the  exudate  being  more 
than  replaced.  The  red  marrow  in  the  shaft  of  the  femur  indicates 
the  great  hyperplasia  of  the  blood-forming  tissue.  The  intense 
congestion  of  an  inflamed  serous  surface  is  shown  in  the  stripped 
pleura.  It  is  difficult  to  separate  the  normal  pleura  from  the  chest 
wall;  in  this  case,  the  separation  is  facilitated  by  the  greater 
saturation  of  the  tissue  with  fluid.  The  exudate  in  the  lung  and 
on  the  pleural  surface  will  be  studied  in  the  histological  section. 
The  spleen  in  this  case  is  unusually  enlarged.  In  most  bacterial 
infections  it  is  enlarged,  the  degree  varying  widely.  The  enlarge- 
ment is  due  chiefly  to  congestion.  The  slight  changes  in  the  liver 
and  kidneys  are  due  to  acute  toxic  degeneration.  The  inflamma- 
tion of  the  middle  ear  is  due  to  bacteria  extending  to  this  by  means 
of  the  eustachian  tube.  The  lines  of  fatty  degeneration  in  the 
intima  of  the  aorta  are  interesting  as  showing  the  relation  which  may 
exist  between  acute  infectious  disease  and  chronic  arterio-sclerosis. 

A  CASE  OF  ORGANIZING  PNEUMONIA  FOLLOWING  ACUTE  WITH  SECOND- 
ARY INFECTION  OF  THE  MENTNGES 

Anatomical  Diagnoses.  Acute  otitis  media;  Acute  cerebrospinal 
meningitis;  Acute  pericarditis;  Unresolved  pneumonia;  Acute 
pleurisy. 

White,  male,  age  two  years.  Body  that  of  a  fairly  well  developed, 
fairly  well  nourished  male.  Rigor  mortis  is  present  and  complete; 


23° 


PATHOLOGY 


there  is  a  moderate  amount  of  lividity  most  marked  in  the  dependent 
parts.  Skin  is  dry  and  smooth.  External  orifices  are  normal.  Abdo- 
men is  considerably  distended  and  tympanitic  throughout.  Pupils 
7  mm.  and  equal. 

Peritoneal  cavity.  The  peritoneum  is  smooth  and  glistening.  Cavity 
contains  a  normal  amount  of  straw-colored  fluid.  Vermiform  appendix 
is  10  cm.  long;  points  upward  behind  the  caecum,  to  which  it  is  closely 
attached;  its  mesentery  is  very  short.  Diaphragm  reaches  the  fourth 
rib  on  the  right,  fourth  interspace  on  the  left  side. 

Pleura!  cavities.  Right  cavity  is  free  from  adhesions.  The  lower 
lateral  aspect  of  this  cavity  has  lost  its  lustre,  has  a  distinct  granular, 
ground-glass  appearance,  and  its  superficial  blood  vessels  are  injected. 
The  left  cavity  shows  numerous,  moderately  firm,  fibrous  adhesions 
which  unite  the  lower  lobe  of  the  lung,  in  its  lateral  and  posterior  aspect, 
to  the  adjacent  pleura. 

Pericardial  cavity.  Pericardium  is  somewhat  increased  in  size,  The 
visceral  layer  is  considerably  thickened  and  has  a  distinct  boggy  feel. 
Upon  opening  the  pericardial  cavity  100  c.c.  of  a  cloudy  fluid  escapes. 
In  this  fluid  are  numerous  gray,  fibrmous  flakes.  Both  visceral  and 
parietal  layers  of  the  pericardium  are  completely  covered  by  a  gray, 
elastic,  rather  dry  exudate.  Over  the  parietal  layer  of  the  pericardium 
this  exudate  averages  about  2  to  3  mm.  in  thickness;  over  the  visceral 
layer  it  is  considerably  thicker. 

Heart  not  opened,  preserved  with  attached  pericardium  for  demon- 
stration. 

Lungs.  Right:  the  lower  lateral  and  posterior  surface  of  the  right 
lobe  has  lost  its  lustre;  shows  a  distinct,  granular,  ground-glass  appear- 
ance. No  areas  of  consolidation  are  demonstrable  in  this  lung.  On 
section  the  lung  is  dark  red  in  color,  and  from  its  surface  a  small  amount 
of  fluid  blood  escapes. 

The  upper  lobe  of  left  lung  is  hyperaemic.  The  lower  lobe  is  firm  and 
resistant.  In  places  it  is  solid,  of  a  yellow  red  color,  not  friable  but 
tough.  The  solidified  areas  are  not  circumscribed  but  pass  without 
outline  into  the  tough  but  not  solidified  surrounding  tissue.  Pieces 
from  the  completely  solid  areas  sink  in  water,  those  from  other  areas 
show  a  varying  degree  of  submergence  and  all  tissue  from  the  lobe 
contains  less  than  the  normal  amount  of  air.  There  is  no  regularity  in 
the  size  or  distribution  of  the  solid  areas. 

Spleen,  weight  65  grams.  It  is  dark  red  in  color.  No  pulp  comes 
away  upon  scraping.  The  trabeculae  and  malpighian  bodies  are  dis- 
tinctly visible. 

Liver,  weight  500  grams.  On  section  it  is  of  a  uniform  pale  color. 
Gall  bladder  and  ducts  are  normal. 


DEPLOCOCCUS  PNEUMONLE  231 

Kidneys,  weight  140  grams.  Capsule  strips  easily  leaving  a  smooth 
surface.  Cortex  bulges  slightly  beyond  the  capsule,  and  measures 
6  mm.  in  thickness.  The  glomeruli  are  distinctly  visible  as  fine  glisten- 
ing points.  The  pyramids  are  dark  red;  the  pelves  and  ureters  are 
normal. 

Adrenals,  pancreas,  bladder,  prostate  and  aorta  normal. 

Gastro-iotestinal  tract.  The  mucosa  of  the  gastro-intestinal  tract 
is  normal.  Mesenteric  lymph  nodes  are  slightly  increased  in  size;  on 
section  are  pale. 

Head.  Scalp  and  calvarium  are  normal.  Dura  is  slightly  adherent 
to  the  calvarium  along  the  great  longitudinal  sinus,  and  strips  easily 
from  the  underlying  pia.  The  great  longitudinal  sinus  contains  a  small 
amount  of  fluid  and  clotted  blood.  The  pacchionian  granulations  are 
normal  in  amount  and  distribution.  The  brain  shows  a  very  marked 
and  very  extensive  exudate  in  the  pia  arachnoid.  This  is  most  pro- 
nounced over  the  base  and  over  the  anterior  half  of  each  cerebral  hemi- 
sphere. The  convolutions  are  broad  and  flattened;  the  sulci  are  in- 
distinct. In  the  anterior  portion  of  the  cerebrum,  where  the  exudate 
is  most  pronounced,  neither  sulci  nor  convolutions  can  be  made  out  as 
the  exudate  so  completely  obscures  them.  This  exudate  is  most  marked 
over  the  left  hemisphere,  about  the  fissure  of  Rolando  and  Sylvius,  and 
over  the  left  temporal  lobe.  The  pons  and  medulla  show  a  very  marked 
yellowish  exudate,  generally  similar  in  character  to  that  covering  the 
lateral  hemispheres,  although  over  the  pons  and  medulla  the  exudate  is 
more  moist.  This  acute  inflammatory  process  extends  over  the  superior 
surface  of  the  cerebellum  and  over  its  internal  and  lower  aspect.  The 
subpial  vessels  throughout  the  brain  are  deeply  injected  and  stand  out 
prominently.  The  brain  substance  is  rather  moist.  The  ventricles 
contain  a  considerable  amount  of  cloudy  fluid,  in  which  numerous  gray 
fibrinous  flakes  are  visible.  The  surface  of  the  ventricles  is  roughened 
and  has  a  granular  appearance.  The  sinuses  at  the  base  of  the  brain 
contain  fluid  and  clotted  blood. 

Middle  ears.  Each  middle  ear  contains  a  considerable  amount  of 
thick  yellowish  exudate. 

Spinal  cord.  The  fat  about  the  dura  shows  marked  injection  of  its 
vessels.  Beneath  the  dura  there  is  a  large  amount  of  cloudy  fluid, 
similar  to  that  seen  within  the  ventricles,  and  the  cord  itself  is  covered 
with  a  yellow  exudate  similar  in  character  to  that  seen  over  the  lateral 
hemispheres. 

Smears  and  cultures  made  from  the  cerebrospinal  fluid,  during  life, 
showed  the  pneumococcus.  Cultures  made  at  autopsy  from  the  surface 
of  the  brain,  ventricles,  middle  ears,  cord,  pericardium,  lungs  (pneu- 
monic area)  and  heart's  blood  showed  the  pneumococcus. 


232  PATHOLOGY 

REMARKS.  The  condition  began  with  an  acute  pneumonia  in 
the  lower  lobe  of  the  left  lung.  The  pneumonia  in  this  case  did  not 
resolve,  that  is,  the  exudate  did  not  undergo  autolysis  but  remained 
and  became  organized,  and  was  replaced  by  connective  tissue. 
The  period  of  this  primary  infection  cannot  be  ascertained.  The 
pneumococcus  infection  persisted  and  has  been  followed  by  various 
extensions;  to  the  middle  ears  on  both  sides,  to  the  meninges,  to 
the  pericardium  and  to  the  pleura.  Meningitis  due  to  the  pneumo- 
coccus is  more  common  in  children  than  in  adults.  It  is  difficult  to 
say  how  infection  extends  to  the  meninges.  It  may  extend  by  the 
blood,  from  the  ears,  or  from  the  nasal  sinuses. 

A  CASE  OF  ORGANIZING  PNEUMONIA 

Anatomical  Diagnoses.  Lobar  pneumonia  (left  lung);  Acute  bi- 
lateral pleuritis;  Organizing  pneumonia  (lower  lobe,  right); 
Acute  splenic  tumor;  Hydropericardium;  Arterio-sclerosis;  Pas- 
sive congestion  of  liver  and  kidneys;  Chronic  fibrous  peritonitis; 
Acute  otitis  media;  Congestion  and  oedema  of  brain;  Cysts  of 
choroid  plexus. 

White,  male,  age  twenty-two  years.  Body  fairly  well  developed, 
nutrition  fair.  Slight  rigor  mortis.  No  oedema.  Subcutaneous  fat  in 
fair  amount. 

Peritoneum.  Appendix  8  cm.  long.  Its  mesentery  extends  to  tip. 
Organ  extends  downward  over  the  brim  of  pelvis.  The  great  omentum 
is  firmly  adherent  to  abdominal  wall  over  a  small  area  in  the  right  iliac 
fossa,  to  the  right  lateral  parietal  wall  and  to  the  gall  bladder.  Mesen- 
teric  lymph  nodes  are  not  increased  in  size. 

Over  both  pleural  surfaces  there  is  a  fibrinous  exudate  with  uniting 
fibrinous  bands.  In  the  right  pleural  cavity  in  places,  the  fibrinous 
adhesions  give  place  to  delicate  bands  of  connective  tissue,  this  being 
most  marked  over  the  posterior  aspect  of  the  lower  lobe. 

Pericardial  cavity.  Shows  slight  increase,  estimated  at  75  c.c.  of 
pericardial  fluid. 

Heart  normal. 

Lungs,  The  left  lung  does  not  contract  on  opening  the  chest.  The 
two  lobes  are  loosely  adherent  by  fibrinous  exudation.  The  lung,  with 
the  exception  of  a  narrow  area  along  the  anterior  border  of  the  upper 
lobe,  is  completely  solidified.  The  upper  lobe  of  an  opaque,  gray  white 
color,  the  lower  redder,  and  this  color  distinction  is  fairly  sharp.  On 
section  of  upper  lobe  the  surface  of  the  section  is  smooth  and  moist  and 


DIPLOCOCCUS  PNEUMONLE  233 

on  pressure  a  thick  viscid  fluid  can  be  expressed.  The  surface  of  section 
of  lower  lobe  is  more  granular  and  drier.  There  is  normal  crepitation 
along  the  anterior  border  of  the  upper  lobe.  The  right  lung,  upper  lobe, 
is  congested,  crepitant  throughout,  somewhat  more  moist  on  section 
than  normal.  The  lower  lobe,  especially  in  lower  half,  is  firmer  than 
normal.  On  section  it  is  generally  firm,  but  there  are  areas  which  are 
tough  and  solid.  These  areas  have  an  indefinite  extension  and  vary  in 
size.  Portions  of  tissue  from  the  centres  sink  in  water.  The  solid 
tissue  cannot  be  torn.  In  color  these  areas  are  distinguished  from  the 
surrounding  congested  lung  tissue  by  a  paler  and  more  yellow  color,  in 
places  the  color  is  almost  golden  yellow. 

Spleen.  Weight  320  grams.  Capsule  smooth.  Tissue  of  flabby 
consistency.  Pulp  soft,  adheres  to  the  knife  and  is  of  a  deep  red  color. 
Neither  trabeculae  nor  follicles  are  visible. 

Intestinal  canal.  Entire  intestinal  canal  normal,  also  the  abdominal 
organs  save  for  congestion  and  cloudy  swelling. 

Brain.  The  pia  arachnoid  is  congested  and  contains  an  excess  of 
fluid.  Easily  stripped  from  convolutions.  The  brain  moist.  Some 
excess  of  fluid  in  the  lateral  ventricles;  in  the  choroid  plexus  there  are 
small  cysts  with  clear  contents. 

Genito-urinary  organs  normal. 

Intima  shows  a  few  yellow  linear  areas  most  marked  in  abdominal 
aorta,  few  being  in  the  arch. 

Right  middle  ear  contains  thick  yellow  pus. 

Both  cultures  and  cover  slip  preparations  from  the  lungs  gave  diplo- 
cocci  for  the  most  part,  as  shown  in  the  smears,  enclosed  in  polynuclear 
leucocytes,  in  culture  morphologically  conforming  to  pneumococci. 

Microscopic  examination  of  the  solidified  areas  in  the  lower  lobe  of 
right  lung  showed  within  the  alveoli  masses  of  thick  fibrin  surrounded 
by  connective  tissue  composed  of  cells  and  fibres.  In  places  this  almost 
filled  the  alveoli,  only  fragments  of  fibrin  being  present.  These  masses 
in  places  were  attached  to  the  alveolar  walls  projecting  as  polypi  into 
the  space.  In  other  places  they  seemed  to  enter  as  a  connected  mass 
from  the  wall  of  terminal  bronchus  filling  the  entire  series  of  spaces 
supplied  by  this.  These  plugs  of  connective  tissue  and  fibrin  contained 
blood  vessels. 

REMARKS.  An  initial  acute  croupous  pneumonia  of  usual 
character  in  the  lower  lobe  of  the  right  lung.  The  exudate  has  in 
part  undergone  the  usual  resolution,  in  part,  as  in  the  solidified 
areas,  it  has  remained  and  is  undergoing  organization.  The  condi- 
tions on  which  this  depends  are  unknown.  The  date  of  this  pri- 


234 


PATHOLOGY 


mary  infection  cannot  be  determined  from  the  histological  examina- 
tion. This  change,  called  carnification  (from  the  resemblance  of 
the  tissue  to  muscle),  may  take  place  in  the  entire  lobe  which  is 
affected,  or  in  focal  areas,  as  in  this  case.  The  infection  of  the  left 
lung  followed,  the  lesions  being  older  in  the  upper  lobe.  The 
lesions  in  other  organs  dependent  upon  the  lung  lesions,  congestion, 
etc.,  need  no  explanation.  The  peritoneal  adhesions  are  evidently 
due  to  a  slight  infection  of  the  peritoneum  of  remote  date  originat- 
ing either  from  the  appendix  or  gall  bladder. 

The  small  cysts  of  the  choroid  plexus  which  are  described  are 
frequently  found  and  seem  to  have  little  or  no  importance  in  dis- 
turbing function. 

A  CASE  OF  ACUTE  SALPINGITIS  PRODUCED  BY  THE 
DIPLOCOCCUS  PNEUMONLE 

The  tubes  with  ovaries  removed  at  operation  and  sent  for  examina- 
tion. The  patient  a  multipara,  no  lesions  discoverable  in  vagina  or 
uterus.  The  tubes  are  enlarged,  the  serous  surface  deeply  injected  and 
cloudy.  The  fimbriae  congested.  On  section  the  entire  wall  is  thickened 
and  oedematous,  the  lumen  dilated  and  contains  abundant,  rather  thick 
pus.  On  section  all  the  vessels  are  dilated,  there  is  mural  accumulation  of 
leucocytes  and  active  emigration  in  the  vessels  of  the  mucous  surface. 
The  epithelium  is  retained  and  both  this  and  the  tissue  beneath  thickly 
infiltrated  with  polynuclear  leucocytes.  These  are  both  between  and 
within  the  epithelial  cells.  There  is  also  considerable  leucocytic  in- 
filtration beneath  the  serous  surface.  Characteristic  diplococci  pneu- 
moniae  were  found  in  cultures  and  smears  and  on  histological  examination. 

REMARKS.  This  case  represents  an  unusual  infection  with  this 
organism.  Both  the  acute  and  the  chronic  forms  of  salpingitis 
usually  are  due  to  the  gonococcus.  Infection  was  most  probably 
from  the  vagina  and  uterus  although  infection  by  the  blood  cannot 
be  excluded. 


DIPLOCOCCUS  INTRACELLULARIS   MENINGITIDIS 

This  is  a  diplococcus  of  the  same  size  as  the  gonococcus,  appear- 
ing as  two  hemispheres  separated  by  an  unstained  interval.  It 
stains  with  any  of  the  ordinary  bacterial  stains,  but  is  decolorized 
by  the  Gram  method.  There  is  considerable  variation  in  the  size 
of  the  organism.  It  does  not  grow  profusely  on  any  of  the  culture 
media,  but  better  on  blood  serum  than  on  any  other  medium.  On 
this  it  forms  white,  shining,  viscid-looking  colonies  with  sharply 
defined  outlines.  The  organism  may  grow  in  bouillon  or  on  various 
solid  media,  but  the  growth  is  feeble. 

It  has  but  feeble  pathogenic  properties  when  inoculated  into 
animals.  Cerebrospinal  meningitis  has  been  produced  in  goats 
and  in  monkeys  by  inoculating  directly  into  the  cerebrospinal 
meninges.  The  organism  is  an  exclusive  parasite.  In  man  the 
organism  produces  the  disease  known  as  epidemic  cerebrospinal 
meningitis.  In  this  there  is  an  exudation  into  the  inner  meninges 
of  the  brain  and  cord.  The  exudate  may  be  purulent,  sero-puru- 
lent,  or  fibrino-purulent.  The  most  marked  lesions  are  found  at 
the  base  of  the  brain,  extending  from  the  optic  commissure  back- 
wards over  the  crura,  the  pons,  and  the  medulla.  The  meninges 
of  the  entire  brain  are  rarely  affected;  the  exudate  on  the  convexity 
is  usually  most  extensive  on  the  lateral  surfaces,  extending  for  some 
distance  on  either  side  of  the  fissure  of  Rolando.  The  exudate 
varies  in  character  according  to  the  acuteness  of  the  process.  In 
the  most  acute  cases  there  is  but  little  exudation,  in  the  more 
chronic  there  is  often  a  considerable  amount,  and  it  contains  a 
great  deal  of  fibrin.  The  exudate  always  contains  numbers  of 
large  endothelial  cells  which  are  phagocytic  for  the  leucocytes. 
In  chronic  cases  there  is  considerable  thickening  of  the  meninges, 
due  to  the  formation  of  granulation  and  connective  tissue.  The 
process  in  the  meninges  of  the  cord  is  the  same  as  in  the  brain.  The 
exudate  ^is  chiefly  in  the  ^meninges  on  the  posterior  surface  of 
the  cord,  and  may  be  confined  to  this  locality.  There  is  proliferation 
of  the  cells  of  the  neuroglia  both  on  the  surface  of  the  brain,  in  and 

235 


236  PATHOLOGY 

beneath  the  ependyma  of  the  ventricles,  and  in  the  vicinity  of  the 
foci  of  softening  and  haemorrhage  in  the  white  and  gray  matter. 
Nuclear  figures  also  are  found  in  the  neuroglia  cells  at  a  distance. 
The  ganglion  cells  of  both  the  brain  and  cord  show  degenerative 
changes. 

From  the  brain  the  exudation  extends  outwards  along  the  various 
cranial  nerves.  The  most  marked  lesions  are  found  in  the  second, 
the  fifth,  and  the  eight  nerves.  In  the  optic  nerve  the  exudate  is 
contained  in  the  pia  arachnoid,  the  subdural  space  of  the  nerve 
being  affected.  The  exudation  may  extend  into  and  destroy  the 
eye.  The  exudation  often  extends  along  the  auditory  nerve  into 
the  internal  ear,  and  from  this  to  the  middle  ear.  It  extends  along 
the  fifth  nerve  to  the  Gasserian  ganglion.  Both  the  nerve  and  the 
ganglion  become  infiltrated  with  the  purulent  exudate,  and  the 
ganglion  cells  are  degenerated.  The  spinal  ganglia  also  show 
purulent  exudate  and  degeneration,  the  process  extending  to  them 
along  the  roots  of  the  spinal  nerves. 

In  a  small  number  of  cases  foci  of  pneumonia,  with  purulent 
exudation  due  to  the  same  organisms  are  found.  The  foci  gen- 
erally are  small. 

It  is  not  known  how  the  organisms  find  entry  into  the  meninges. 
In  a  few  cases  acute  coryza  has  been  found,  and  it  has  been  sup- 
posed that  the  cocci  may  make  their  way  into  the  meninges  from 
the  nose  by  means  of  the  lymphatics.  The  number  of  micrococci 
found  varies  greatly  in  the  different  cases,  but  they  always  are 
more  abundant  in  the  more  acute  cases.  They  are  almost  exclu- 
sively found  within  the  polymorphonuclear  leucocytes.  The  few 
which  are  found  outside  the  cells  in  smears  from  the  exudate  come 
from  cells  which  are  ruptured  in  making  the  preparation.  They 
also  may  be  found  in  considerable  numbers  hi  the  exudate  from 
the  middle  ear  when  this  is  involved  by  the  extension  of  infection 
from  the  meninges.  The  organisms  are  found  in  much  greater 
numbers  in  the  focal  pneumonia  accompanying  meningitis  than  in 
the  exudation  in  the  meninges.  The  infection  of  the  lungs  is 
secondary  to  the  infection  of  the  meninges,  the  cocci  reaching  the 
lungs  either  by  the  blood  or  by  the  bronchi  after  preceding  infection 
of  the  middle  ear  and  Eustachian  tube. 

Other  infections  by  this  organism,  both  in  connection  with  men- 
ingitis and  independently,  occur,  but  they  are  rare. 


DIPLOCOCCUS  INTRACELLULARIS  MENINGITEDIS        237 

A  CASE  OF  ACUTE  EPIDEMIC  CEREBROSPINAL  MENINGITIS. 
Anatomical  Diagnosis.    Acute  epidemic  cerebrospinal  meningitis. 

White,  male,  age  two  years.  On  December  ist,  the  child  was  supposed 
to  have  fallen  from  a  trunk  or  to  have  been  knocked  down  by  a  suddenly 
opened  door.  This  happened  at  5  P.M.  Child  ate  supper,  and  slept 
fairly  well.  The  next  morning  refused  to  eat,  became  unconscious  at 
9  A.M.,  and  remained  so  until  death.  At  n  A.M.,  had  a  tonic  convul- 
sion which  lasted  one  minute,  all  extremities  being  equally  affected.  In 
the  following  eight  hours  had  ten  similar  convulsions  and  vomited 
several  times.  At  8  P.M.,  December  2,  lumbar  puncture  was  done  and 
40  c.c.  of  turbid  fluid  obtained,  the  fluid  being  under  increased  pressure. 
Death,  a  few  hours  later. 

Body  well  developed  and  well  nourished.  Lividity  of  skin  marked  in 
the  posterior  dependent  portions  of  trunk  and  extending  to  the  face  and 
front  of  chest.  The  anterior  surface  of  chest  shows  decided  mottling 
of  the  skin,  but  no  evident  eruption.  Slight  rigor  mortis. 

All  the  organs  of  the  body  perfectly  normal  with  the  exception  of  the 
brain.  The  bladder  was  distended  and  reached  half  way  to  the  umbilicus. 

Head.  Anterior  fontanelle  open,  sagittal  and  coronal  sutures  not  yet 
fused.  Sinuses  contain  fresh  blood  clots.  The  inner  surface  of  dura 
moistened  by  a  slight  amount  of  yellowish  fluid  exudation.  There  is  a 
thick  purulent  exudate  hi  the  pia  arachnoid,  most  marked  along  the 
course  of  the  vessels.  The  exudate  is  most  abundant  at  the  base  of  the 
brain  and  over  the  superior  surfaces  of  the  parietal  lobes.  The  cortex 
in  contact  with  the  exudate  is  slightly  injected  and  softer.  The  vessels 
of  the  pia  greatly  congested.  The  lateral  ventricles  contain  a  turbid 
blood-stained  fluid.  The  basal  ganglia  are  unchanged. 

Spinal  cord.  The  pia  of  the  entire  cord  is  cloudy  and  lustreless.  In 
the  lumbar  region  beneath  the  dura  there  is  a  considerable  amount  of 
cloudy  blood-stained  fluid. 

Smears  and  cultures  from  the  exudation  showed  abundant  Gram 
negative  diplococci.  In  the  smears  they  were  chiefly  within  the  poly- 
nuclear  leucocytes. 

REMARKS.  A  very  typical  case  of  acute  epidemic  cerebro- 
spinal meningitis.  The  clinical  history  is  given  to  show  how  short 
period  of  symptoms  may  be.  It  is  very  possible  that  the  fall  which 
was  described  may  mark  the  first  symptom,  or  it  may  have  no 
relation  to  the  attack.  The  exudate  is  unusually  large  for  so 
acute  a  case. 


GONOCOCCUS 

This  is  a  coccus  occurring  always  in  pairs,  the  single  cocci  flattened 
slightly  at  the  side  of  contact.  It  is  an  exclusive  parasite  of  man. 
The  organism  is  cultivated  with  difficulty  and  only  on  special 
media.  The  temperature  limits  of  growth  are  30  and  38°  C. 

The  urethra  of  the  male  and  female,  the  conjunctiva  in  the  new- 
born, the  vagina,  uterus  and  tubes  are  the  most  susceptible  tissues. 
Infection  is  almost  invariably  through  coitus.  The  infection  may 
extend  from  the  urethra  in  the  male  to  the  prostate  and  epididymes, 
and  in  the  female  to  the  uterus,  the  tubes  and  the  glands  of  Bartho- 
lin.  Local  peritonitis  involving  the  pelvic  peritoneum  and  resulting 
in  extensive  adhesions  results  from  extension  of  infection  from  the 
Fallopian  tubes.  Extension  to  the  bladder  and  kidneys  occurs 
but  is  not  common.  The  organism  may  enter  into  the  blood  and 
be  carried  to  the  joints,  the  synovial  membrane  being  susceptible 
to  the  action  of  the  organism.  Acute  endocarditis  may  be  pro- 
duced also.  These  remote  infections  are  more  common  in  the 
male,  probably  owing  to  the  better  opportunity  for  blood  infection. 

The  infection  of  the  Fallopian  tubes  produces  serious  and  ex- 
tremely chronic  conditions.  The  tubes  in  the  chronic  state  are 
enlarged  and  tortuous,  the  wall  greatly  thickened  by  an  increase 
in  tissue  and  oedema.  The  exterior  surface  frequently  is  covered 
with  adhesions  and  these  may  mat  together  uterus,  tubes  and 
ovaries.  The  lumen  is  dilated,  the  papillary  folds  of  mucous 
membrane  are  irregular  and  the  epithelium  may  be  in  large  measure 
lost.  Leucocytes,  desquamated  epithelial  cells  and  large  endothe- 
lial  cells  containing  fat  are  found  in  the  lumen.  Beneath  the  surface 
are  large  numbers  of  plasma  and  lymphoid  cells.  In  the  wall  are 
foci  of  lymphoid  cells  which  may  take  the  form  of  definite  lymph 
nodes  with  germinal  centres  and  sinuses. 

In  acute  infections  gonococci  are  found  in  large  numbers  and 
chiefly  in  the  pus  cells.  In  the  chronic  infections  they  are  difficult 
to  find.  Apparently  a  very  low  grade  of  infection  is  present  in 
chronic  cases,  few  organisms  with  a  very  low  degree  of  virulence 
living  on  the  surfaces,  as  the  staphylococcus  may  live  on  the  skin, 

238 


GONOCOCCUS 


239 


but  the  gonococci  from  these  cases  when  implanted  on  a  fresh  soil 
can  quickly  regain  virulence. 

A  CASE  OF  GONORRHEA  WITH  GENERALIZATION  or  THE  INFECTION 

Anatomical  Diagnoses.  Acute  gonorrheal  urethritis,  prostatitis, 
synovitis,  pericarditis,  myocarditis  and  endocarditis;  Perforation 
of  the  heart;  Haemorrhage  into  pericardium. 

White,  male,  age  thirty  years,  admitted  to  hospital  September  3Oth. 
A  urethral  discharge  noticed  four  weeks  before  admission.  Ten  days 
after  this  the  left  knee  began  to  swell  and  became  painful.  After  four 
days  the  right  knee  became  similarly  affected.  Since  this  he  has  had 
pain  and  swelling  in  fingers,  shoulder  and  ankles.  There  is  pain  in  the 
chest  on  deep  inspiration.  On  October  6th,  pain  in  chest  ceased.  On 
October  yth,  he  complained  of  increased  pain  in  chest.  There  was  a 
slight  increase  in  cardiac  dullness,  no  murmur  or  pericardial  rub.  Octo- 
ber 8th,  continued  pain  in  chest;  October  Qth,  slept  well,  awoke  at  6 
o'clock  and  drank  some  milk.  At  7  o'clock  he  cried  out  as  if  in  pain  and 
fell  out  of  bed.  The  house  officer  found  him  gasping  for  breath  and  no 
pulse  perceptible  at  wrist.  Died  immediately  after  being  seen.  The 
temperature  during  the  whole  course  of  the  attack  did  not  exceed  99^. 
The  pulse  was  under  no. 

Autopsy  twenty-six  hours  after  death.  The  body  of  medium  size, 
slightly  built,  badly  nourished.  The  general  surface  cyanotic.  Both 
knee  joints,  especially  the  right,  enlarged  and  fluctuation  is  evident. 
The  subcutaneous  fat  small  in  amount,  muscles  pale. 

Peritoneum  smooth.     No  adhesions.    Both  lungs  free  from  adhesions. 

The  pericardium  enormously  distended.  The  external  surface  con- 
gested and  covered]  with  small  haemorrhagic  foci.  In  the  pericardial 
cavity  there  is  800  c.c.  of  bloody  fluid  in  which  there  are  large  masses  of 
clot.  On  removal  of  this  both  the  surfaces  of  the  pericardium  are 
covered  with  fibrinous  exudation  containing  foci  of  haemorrhage. 

The  heart  is  firmly  contracted.  The  myocardium  of  left  ventricle  is 
firm  and  in  places  of  a  peculiar  waxy  color  somewhat  resembling  amyloid. 
About  the  bases  of  the  papillary  muscles  the  tissue  has  a  gray  translucent 
gelatinous  appearance.  This  is  especially  marked  at  the  apex  of  the 
ventricle  and  in  places  is  associated  with  hemorrhage.  This  condition 
of  the  myocardium  is  almost  confined  to  the  left  ventricle.  There  is 
some  evidence  of  it  on  the  right  side,  but  it  is  not  so  well  marked.  On  the 
interior  surface  of  the  left  auricle  there  is  an  area  2  by  2.5  cm.  where  the 
muscular  tissue  is  pale,  opaque  and  softened.  In  the  centre  of  this  there 


240  PATHOLOGY 

is  an  irregular,  small  perforation  2  mm.  in  diameter.  The  valves  are 
normal,  the  coronary  arteries  smooth. 

The  spleen  is  enlarged,  the  follicles  prominent. 

Liver  and  kidneys  slightly  enlarged  and  cloudy. 

Pancreas  normal. 

Gastro-intestinal  canal.  Stomach  normal.  All  the  follicular  tissue 
in  large  and  small  intestine  is:  enlarged  -and  hyperaemic.  In  the  small 
intestine  the  single  follicles  project  almost  as  small  polypi.  The  Peyer's 
patches  are  enlarged  and  smooth  on  the  surface.  All  the  mesenteric 
lymph  nodes  are  enlarged. 

The  lungs  are  hyperaemic  with  slight  oedema  in  posterior  portions. 
Bronchial  lymph  nodes  slightly  enlarged. 

The  right  knee  joint  is  greatly  distended.  On  section  about  100  c.c. 
of  viscid,  rather  transparent  pus  escapes.  The  synovial  membrane  of 
joint  swollen  and  intensely  congested.  Papillary  fungoid  masses  of 
granulation  tissue  extend  into  the  joint  from  the  synovia,  having  some- 
what the  appearance  of  tuberculous  granulations.  These  masses  have 
a  pale  and  opaque  surface  and  below  this  the  tissue  is  cedematous.  The 
muscles  in  the  vicinity  of  the  joint  are  cedematous.  The  left  knee  joint 
is  similarly  affected. 

Genito-urinary  system.  Bladder  somewhat  distended,  mucous  mem- 
brane pale  and  normal.  The  entire  mucous  surface  of  the  urethra  is 
thickened  and  dense.  About  4  cm.  from  the  meatus  there  is  a  slight 
loss  of  substance  on  the  surface.  The  mucous  surface  is  covered  with  a 
slight  purulent  exudate.  The  prostate  is  enlarged.  On  section  there  is 
a  general  purulent  infiltration  of  the  tissue  and  on  the  left  side  a  distinct 
abscess.  The  seminal  vesicles,  testicles,  and  epididymes  show  no 
alteration. 

Microscopic  examination  of  the  pericardial  exudation  shows  in  addi- 
tion to  the  blood  large  numbers  of  pus  cells  and  large  endothelial  cells. 
No  gonococci  are  found  in  the  pus  of  the  exudate.  The  examination 
of  coverslips  from  the  urethra,  from  the  knee  joint  and  from  the  abscess 
in  the  prostate  shows  gonococci.  They  are  abundant  in  the  urethra,  but 
comparatively  few  are  found  in  the  joint.  The  organisms  are  contained 
only  in  pus  cells  and  morphologically  and  in  staining  are  identical  with 
gonococci. 

Microscopic  examination  of  sections  of  the  urethra  shows  here  and 
there  slight  losses  of  substance  in  the  mucous  membrane.  Among  the 
epithelial  cells  there  are  numbers  of  polynuclear  leucocytes  and  many 
of  these  on  the  surface  contain  gonococci  in  characteristic  arrangement. 
The  tissue  immediately  beneath  the  mucous  surface  along  almost  the 
entire  length  of  the  urethra  shows  an  intense  infiltration  with  lymphoid 


GONOCOCCUS  241 

and  plasma  cells.  No  gonococci  are  found  in  the  submucous  tissue  nor 
in  the  deep  layers  of  the  epithelium.  The  cells  of  the  mucous  membrane 
throughout  are  swollen,  more  or  less  desquamated,  and  in  places  entirely 
absent,  the  granulation  tissue  appearing  on  the  surface.  The  gonococci 
are  more  abundant  where  the  purulent  infiltration  of  the  tissue  is  most 
intense.  They  are  found  in  the  crypts  of  Morgagni,  but  are  .less  numer- 
ous here  than  on  the  surface.  Sections  of  the  membranous  portion  of 
the  urethra  near  the  prostate  show  the  same  condition.  In  the  ducts  of 
the  prostate  there  is  a  purulent  exudate  with  but  few  gonococci.  The 
prostatic  tissue  shows  an  intense  purulent  infiltration  with  focal  destruc- 
tion of  epithelium.  On  one  side  the  tissue  is  softened  and  broken  down 
into  an  abscess. 

Sections  from  the  heart  show  an  intense  pericarditis.  The  pericardium 
is  thickened,  swollen  and  infiltrated  with  polynuclear  leucocytes.  In 
places  there  are  small  amounts  of  fibrin  on  the  surface.  In  the  most 
degenerated  part  of  the  myocardium  of  the  left  ventricle,  there  is  exten- 
sive purulent  infiltration  and  necrosis  of  muscle  fibres.  In  places  the 
exudate  is  distinctly  haemorrhagic  in  character.  In  the  left  auricle  there 
is  a  large  area  of  necrosis  and  purulent  infiltration  which  involves  the 
entire  thickness  of  the  wall.  In  this  area  there  are  great  numbers  of 
gonococci  within  the  pus  cells.  In  the  area  around  the  rupture  necrosis 
of  the  myocardium  is  complete. 

The  sections  of  the  granulation  tissue  in  the  knee  joint  show  a  purulent 
exudation  on  the  surface  extending  a  short  distance  into  the  tissue. 
Below  this  the  tissue  is  of  the  type  of  very  vascular  connective  tissue. 
Gonococci  are  found  in  small  numbers,  never  deep  in  the  tissue,  but 
always  immediately  on  the  surface  or  in  the  most  superficial  layers. 

REMARKS.  The  case  is  primarily  one  of  gonorrheal  infection. 
The  urethral  lesions  show  a  purulent  exudation  with  acute  degener- 
ation and  desquamation  of  the  mucous  surface  and  a  very  marked 
reaction  in  the  tissue  beneath.  The  condition  involves  the  entire 
urethral  surface  including  the  urethral  pouches.  The  gonococci 
are  confined  to  the  surface  and  are  in  the  interior  of  the  pus  cells; 
the  infection  has  extended  from  the  urethra  into  the  prostate. 
More  frequently  the  extension  is  into  the  epididymis.  It  is  easy 
to  understand  from  the  situation  of  the  gonococci  the  persistency 
of  gonorrheal  infection,  for  in  the  crypts  of  the  mucous  membrane 
they  cannot  be  reached  by  therapeutic  applications.  Infection 
of  the  joints  by  way  of  the  blood  is  not  uncommon  in  gonorrhea. 
Here  much  the  same  conditions  are  produced  as  in  the  urethra. 


242  PATHOLOGY 

The  gonococci  grow  on  the  surface  and  do  not  invade.  The  condi- 
tion of  the  heart  is  interesting.  There  is  here  an  acute  pericarditis 
with  a  fibrino-purulent  exudate.  The  pain  which  the  patient  com- 
plained of  in  the  pericardial  region  is  due  to  this.  The  evidence  of 
the  exudation  is  also  seen  in  the  increased  dullness  over  the  cardiac 
area.  The  infection  of  the  myocardium  resulting  in  increased 
purulent  infiltration  and  haemorrhage  is  an  unusual  manifestation 
of  the  gonorrheal  infection.  The  valves  of  the  heart  are  more 
frequently  the  site  of  the  infection.  The  perforation  of  the  heart 
through  the  softened  area  in  the  auricle  took  place  probably  a  few 
minutes  before  the  death  of  the  patient  adding  the  haemorrhage  to 
the  mass  of  pericardial  fluid,  the  pressure  from  which  was  already 
interfering  with  the  heart's  action.  It  is  also  interesting  to  see 
the  large  amount  of  fluid  which  was  in  great  part  not  due  to  the 
haemorrhage  but  to  the  exudation. 


BACILLUS  TUBERCULOSIS 

Although  four  types  of  the  tubercle  bacilli  are  recognized,  the 
human,  the  bovine,  the  fowl  and  the  piscian,  only  the  human  and 
the  bovine  are  pathogenic  for  man.  These  two  types  are  differen- 
tiated by  their  cultural  peculiarities,  their  infectiousness  and  to 
some  extent  by  their  morphology.  The  human  bacilli  grow  more 
readily  than  the  bovine,  the  surface  of  the  growth  is  dryer  and  more 
nodular  and  they  are  less  pathogenic  for  laboratory  animals,  par- 
ticularly the  rabbit,  than  are  the  bovine  bacilli.  Morphologically 
the  human  bacilli  are  somewhat  longer  and  show  more  variation 
in  size  than  do  the  bovine. 

The  tubercle  bacilli  are  slender  rods  usually  somewhat  curved 
and,  in  the  tissues,  tend  to  occur  in  small  groups  of  as  many  as  a 
dozen,  the  single  bacilli  often  parallel,  or  in  large  masses.  They 
are  found  both  within  cells  and  free.  The  bacillus  is  a  parasite 
only,  adapted  for  a  certain  narrow  environment.  It  is  the  type 
of  the  acid  fast  bacilli,  stains  penetrate  the  outer  covering  with 
difficulty  and  are  not  removed  by  the  action  of  acids.  Of  the 
laboratory  animals  the  guinea  pig  is  the  most  susceptible.  The 
fluid  of  cultures  free  from  bacilli  has  slight  pathogenic  properties, 
but  the  chief  action  of  the  organisms  is  due  to  endotoxines. 

The  mode  of  infection  in  man  is  obscure  and  the  bacilli  can  enter 
by  a  number  of  routes.  It  usually  is  assumed,  from  the  frequency 
and  the  extent  of  the  lesions  in  the  lungs,  that  infection,  in  the 
majority  of  cases,  takes  place  by  inhalation  of  bacilli.  The  bacilli 
can  enter  the  body,  without  the  production  of  lesions  at  the  point 
of  entry,  and  be  carried  to  remote  parts,  such  as  the  bones  or  lymph 
nodes,  and  there  produce  lesions.  Infection  may  take  place  from 
the  mucous  membrane  of  the  mouth  and  the  alimentary  canal. 
The  organism  may  also  enter  the  skin  by  means  of  the  natural 
openings,  or  through  lesions  produced  by  trauma.  Infection  by 
the  skin  plays  but  little  part  in  the  disease  although  local  lesions 
may  be  produced.  Infection  through  the  placenta  can  take  place, 
but  is  infrequent.  Bacilli  have  been  found  in  lesions  of  the  placenta 
and  in  the  tissues  of  the  foetus;  extensive  lesions  have  also  been 

243 


244  [PATHOLOGY 

ound  in  the  organs  of  children  so  young  that  placental  infection 
fmust  be  assumed. 

Susceptibility  to  infection  seems  to  vary  in  different  individuals. 
Certain  families  are  more  prone  to  the  disease.  The  great  fre- 
quency of  tuberculous  lesions,  which  is  found  at  autopsies  (safely 
reckoned  at  two  thirds  of  all  adults)  and  the  great  frequency  with 
which  healed  lesions  are  found,  show  that  the  differences  in  indi- 
viduals is  rather  a  matter  of  tissue  resistance  to  the  extension  of  the 
tuberculous  process,  than  of  resistance  to  infection.  The  general 
resistance  varies  at  different  ages  and  at  different  periods  in  the 
course  of  the  disease.  The  chronic  forms  of  tuberculosis  tend  to 
remain  quiescent  for  considerable  periods  and  then  to  extend  sud- 
denly. The  different  tissues  of  the  body  vary  greatly  in  their 
resistance  to  the  action  of  the  bacilli.  The  muscles,  the  brain, 
the  ovaries,  the  testicles  and  the  pancreas  are  the  most  resistant 
tissues.  These  tissues  rarely  are  primarily  attacked  but  may  be 
affected  by  the  extension  of  a  tuberculous  process  in  the  vicinity. 

The  usual  effect  produced  by  the  tubercle  bacilli  is  proliferation 
of  the  fixed  cells  of  the  tissue  with  the  production  of  large  cells  of 
the  endothelial  type.  These  cells  may  be  formed  from  connective 
tissue  cells,  from  certain  epithelia  as  the  epithelium  of  the  lung 
alveoli,  and  from  the  endothelial  cells  of  the  blood  and  lymphatic 
vessels.  It  is  probable  that  they  most  frequently  are  of  endothelial 
origin.  The  tubercle  bacilli  are  found  both  in  and  between  these 
cells.  Associated  with  these  cells  are  giant  cells.  These  are  large 
protoplasmic  masses  with  a  number  of  nuclei  which  are  arranged 
either  at  the  extremities  of  elongated  cells  or  around  the  periphery 
of  round  or  irregular  cells.  Giant  cells  are  so  commonly  present 
that  they  constitute  one  of  the  landmarks  by  which  tuberculous 
tissue  is  recognized.  Giant  cells  are  formed  from  the  fusion  of 
large  endothelial  cells.  Between  these  cells  there  is  often  the 
appearance  of  reticulum.  This  reticulum  is  in  part  connective 
tissue  representing  the  old  connective  tissue  between  the  original 
cells  and  in  part  is  newly  formed.  The  appearance  of  reticulum 
is  often  given  by  the  extension  of  the  branched  processes  of  the 
giant  cells. 

MILIARY  TUBERCLE.  Such  a  tissue,  composed  of  endothelial  and 
giant  cells  with  or  without  a  reticulum,  may  be  present  in  small 
masses  from  o.i  to  i  mm.  in  diameter.  They  never  contain  blood 


BACILLUS  TUBERCULOSIS'  245 

vessels  and  have  a  pale  gray  color.  The  disease  tuberculosis  takes 
its  name  from  the  presence  of  these  small  nodules  or  tubercles. 
Around  the  periphery  of  the  tubercle  a  tissue  is  formed  containing 
cells  similar  to  those  of  granulation  tissue,  namely,  lymphoid, 
plasma  and  endothelial  cells.  Degenerative  changes  in  the  tubercle 
are  constant.  There  is  fatty  degeneration  of  the  central  cells  and 
of  the  giant  cells,  which  may  be  recognized  in  fresh  sections  by 
fat  stains.  The  most  characteristic  form  of  degeneration  is  that 
known  as  caseation.  In  this  the  contour  of  the  individual  cells  is 
lost  and  they  become  fused  together  into  a  soft,  granular  mass 
containing  nuclear  fragments.  The  caseation  often  is  preceded 
by  fatty  degeneration,  a  fatty  ring  appearing  around  the  central 
caseous  mass.  Even  in  the  giant  cells  caseation  takes  place  in  the 
centre,  often  surrounded  by  .a  fatty  ring.  The  giant  cell  in  this 
way  in  itself  represents  a  type  of  a  tubercle.  Leucocytes  enter  into 
the  formation  of  the  tubercle  only  when  the  central  caseation  takes 
place,  and  may  be  found  around  the  periphery  of  the  caseous  mass. 

CONGLOMERATE  TUBERCLE.  Miliary  tubercles  tend  to  increase 
in  size  by  peripheral  growth  to  only  a  very  limited  degree.  This 
may  be  due  to  the  fact  that  the  cells  at  the  periphery  gradually 
acquire  a  resistance  to  the  action  of  the  bacilli.  The  increase  in 
size  of  the  nodule  is  by  continuous  formation  of  miliary  tubercles  in 
the  periphery.  This  is  due  to  the  conveyance  of  tubercle  bacilli 
from  the  parent  nodule  into  the  surrounding  tissue  where  they  set 
up  similar  centres  of  growth.  In  this  way  nodules  of  considerable 
size  may  be  formed,  the  whole  centre  becoming  caseous  by  the  ex- 
tension and  fusion  of  the  caseous  centres  of  the  individual  tubercles. 
Most  of  the  tubercles  which  are  large  enough  to  be  seen  by  the 
naked  eye  are  conglomerate  in  character.  Very  large  conglomerate 
tubercles  tend  to  form  in  resistant  tissues  as  in  the  brain. 

DIFFUSE  TUBERCULOUS  TISSUE.  The  same  sort  of  tissue  which 
is  found  hi  the  miliary  tubercle  may  form  diffuse  masses.  There 
is  not  a  sharp  separation  between  such  a  mass  and  the  surrounding 
tissue.  Giant  cells  in  variable  numbers  may  form  among  the 
endothelial  cells,  more  generally  at  the  edge  of  the  area.  Irregular 
areas  of  caseation  appear,  the  single  areas  often  joining  and  form- 
ing a  network  through  the  tissue.  The  best  examples  of  such 
diffuse  formation  of  tuberculous  tissue  is  found  in  large  tuberculous 
lymph  nodes  and  in  tuberculous  synovitis. 


346  PATHOLOGY 

TUBERCULOUS  EXUDATE.  With  cell  proliferation  in  tuber- 
culosis there  is  exudation  to  a  greater  or  less  degree.  The  amount 
and  character  of  the  exudate  varies;  it  may  be  so  abundant  that 
it  is  the  most  prominent  change  and  masks  the  proliferation;  it 
may  be  composed  of  polynuclear  leucocytes  and  have  all  of  the 
properties  of  the  purulent  exudation.  Very  commonly  there  is 
considerable  fibrin  in  the  exudate  and  the  remains  of  fibrin  may  be 
found  in  caseous  tissue.  In  the  lungs  there  is  often  found  a  peculiar 
sort  of  serous  exudation.  In  this  the  alveoli  are  filled  with  a  viscid, 
more  or  less  gelatinous,  clear,  transparent  material.  This  is  not 
peculiar  to  tuberculosis,  but  is  found  more  commonly  in  association 
with  this  than  with  any  other  process.  Tuberculous  exudates  are 
found  more  commonly  in  certain  parts  of  the  body  than  others 
and  are  especially  prominent  when  surfaces  are  affected.  In 
tuberculosis  of  the  lungs,  the  meninges  and  serous  surfaces,  there 
usually  is  a  large  amount  of  exudate.  In  the  lungs  just  as  definite 
fibrinous  exudate  may  be  found  in  the  air  spaces  as  after  infection 
with  the  pneumococcus.  Miliary  tubercles  may  form  on  surfaces 
and  afterwards  be  covered  by  an  exudate.  Red  blood  corpuscles 
may  be  so  abundant  in  the  exudate  as  to  give  it  a  haemorrhagic 
character.  In  tuberculous  pneumonia  the  exudate  undergoes  the 
same  fate  as  the  tuberculous  tissue.  It  does  not  undergo  autoly- 
sis,  but  becomes  caseous.  The  large  caseous  areas  found  in  the 
lung  are  due  rather  to  caseation  of  the  exudate  and  the  tissue  which 
contains  it  than  to  the  caseation  of  definite  tuberculous  tissue. 

CICATRIZATION.  Around  the  tubercle  there  is  a  tendency  to  the 
formation  of  cicatricial  connective  tissue  which  is  resistant  to  the 
action  of  the  bacilli  and  tends  to  prevent  the  extension  of  the 
process.  The  more  resistant  the  animal  and  the  tissue  the  greater 
is  the  tendency  to  the  formation  of  cicatricial  tissue.  This  is  dense, 
resistant,  contains  few  blood  vessels  or  spaces  by  which  the  bacilli 
can  pass  the  encircling  wall,  and  also  few  cells.  Such  a  tissue  can 
be  formed  inside  of  the  tubercle  by  the  formation  of  intercellular 
substances  from  the  cells  comprising  its  structure.  This  tissue  can 
also  become  caseous,  but  the  caseous  mass  is  firm  and  differs  from 
that  formed  by  degeneration  of  the  cells.  Tuberculosis  does  not 
heal  by  the  destruction  of  bacilli  or  their  removal,  but  by  connective 
tissue  masses  forming  a  resistant  wall  around  the  lesion.  It  is  not 
uncommon  to  find  in  the  lungs,  or  elsewhere  in  the  body,  masses 


BACILLUS  TUBERCULOSIS  247 

of  tuberculous  tissue  which  have  undergone  caseation  and  become 
walled  off  by  a  firm  mass  of  cicatricial  tissue.  It  is  not  known 
how  long  tubercle  bacilli  can  live  enclosed  in  such  a  mass.  The 
most  rapidly  fatal  forms  of  tuberculosis  are  those  in  which  the 
exudative  processes  form  the  chief  lesions. 

The  mass  formed  by  the  caseation  of  tuberculous  tissue  and 
exudate  may  remain  in  an  unchanged  condition.  When  composed 
chiefly  of  cells  it  is  soft  and  easily  broken  down,  but  is  firmer  if 
connective  tissue  has  entered  into  its  formation.  Lime  salts  may 
be  deposited  in  the  caseous  material  and  the  nodule  become  calci- 
fied. This  is  a  conservative  process  and  tends  further  to  prevent 
dissemination.  A  much  more  unfavorable  process  is  softening. 
By  this  the  comparatively  firm,  caseous  mass  becomes  changed 
into  a  soft,  semifluid  material.  It  is  not  absolutely  known  upon 
what  this  softening  depends.  It  may  be  due  to  the  action  of 
ferments  within  the  caseous  material,  as  hi  the  softening  of  the 
thrombus,  or  it  may  result  from  the  action  of  other  organisms 
which  secondarily  invade.  The  great  danger  of  tuberculous 
softening  is  that  the  softened  material,  carrying  the  bacilli,  may 
find  its  way  into  the  adjoining  normal  tissue  extending  the  infection. 

THE  RELATIONS  OF  TUBERCLE  BACILLI  TO  THE  PROCESS.  The 
number  of  tubercle  bacilli  which  are  found  in  the  lesions  varies 
enormously.  They  are  present  in  the  greatest  numbers  where  the 
process  is  most  active  and  most  exudative  in  character.  Large 
numbers  may  be  found  within  the  endothelial  cells  or  within  the 
giant  cells.  When  tubercles  develop  in  resistant  tissue,  very  few 
bacilli  will  be  found.  In  certain  cases  they  may  be  found  in  the 
tissues  without  any  reaction  about  them.  Very  few  are  found  in 
old  lesions  enclosed  hi  cicatricial  tissue.  That  they  are  contained 
in  such  tissue  is  shown  by  its  infectiousness  when  injected  into  a 
susceptible  animal. 


FORMS   OF  TUBERCULOSIS 

GENERAL  MILIARY  TUBERCULOSIS.    In  nearly  all  cases  of  tuber- 
culosis a  few  bacilli  enter  into  the  blood  and  are  carried  by  this  into 
distant  organs.    In  miliary  tuberculosis  the  tubercle  bacilli  usually 
are  carried  into  the  tissue  by  the  blood  route.    Large  numbers  of 
bacilli  entering  into  the  circulation  are  carried  into  all  of  the  tissues 
and  give  rise  to  the  formation  of  great  numbers  of  small  tubercles. 
These  are  most  abundant  in  the  lungs,  liver,  spleen  and  on  serous 
surfaces.    They  are  less  abundant  in  the  kidneys  and  usually  are 
absent  in  the  brain,  the  wall  of  the  alimentary  canal,  the  muscles 
and  the  skin.    Such  a  general  infection  takes  place  from  some 
focus  in  the  body  where  the  tuberculous  tissue  is  in  the  interior  of 
the  vessels.    This  may  be  due  either  to  the  extension  of  tuber- 
culosis outside  of  the  vessel  or  to  infection  of  the  endothelium.    In 
the  latter  case  large  mural  thrombi  may  be  formed  within  the 
vessel;   the  bacilli  find  in  the  masses  of  thrombus  suitable  condi- 
tions for  growth,  and  from  this  source  either  an  instantaneous  ex- 
tension of  the  bacilli  into  the  circulation  takes  place,  or  they  may 
pass  into  the  circulation  at  intervals.    In  rare  cases  such  an  enor- 
mous number  of  tubercle  bacilli  may  be  found  in  the  circulation 
that  it  seems  evident  that  they  multiply  in  the  blood  or  in  the 
endothelial  cells  at  numerous  places.     Cases  also  are  found  in 
which  there  is  extensive  tuberculosis  of  the  thoracic  duct  from 
which  place  the  bacilli  can  enter  the  circulation.     In  certain  cases 
a  tuberculous  aneurysm  forms.    In  this  the  tuberculous  focus  is 
formed  on  the  exterior  of  the  vessel  the  infection  coming  from  one 
of  the  vasa  vasorum  or  from  a  tuberculous  lymph  node.     By  the 
extension  of  the  process  to  the  wall  of  the  vessel,  this  becomes 
weakened  and  a  tuberculous  aneurysm  is  formed.    Both  in  the  wall 
of  the  aneurysm  and  in  the  thrombus  which  it  contains  there  may 
be  immense  numbers  of  bacilli  which  easily  enter  the  blood.    The 
formation  of  acute  miliary  tuberculosis  does  not,  however,  depend 
solely  upon  the  opportunity  of  infection  by  means  of  the  blood. 
Rarely  cases  are  seen  in  which  large  numbers  of  tubercle  bacilli 
may  be  demonstrated  in  the  circulation  without  the  formation  of 

248 


FORMS  OF  TUBERCULOSIS  249 

miliary  tubercles.  In  these  cases  it  must  be  assumed  that  either 
the  tubercle  bacilli  are  devoid  of  virulence  or  that  the  tissues  are 
resistant  to  their  action.  In  the  most  marked  cases  of  acute  miliary 
tuberculosis  the  disease  runs  its  course  in  a  very  short  time,  with 
fever  and  the  general  clinical  characteristics  of  an  acute  infectious 
disease,  and  the  organs  are  filled  with  very  small  gray  miliary  tub- 
ercles in  most  of  which  caseation  has  not  yet  taken  place.  In  con- 
tradistinction to  the  cases  in  which  the  resistance  of  the  tissue  is 
apparently  high,  rapid  cases  are  encountered  in  which  the  tubercles 
take  the  form  of  small  foci  of  exudation  often  combined  with  single 
giant  cells  and  contain  numbers  of  bacilli. 

CHRONIC  MILIARY  TUBERCULOSIS.  In  certain  cases  the  disease 
runs  a  more  chronic  course,  the  tubercles  are  not  so  numerous,  are 
larger  and  more  advanced  in  caseation.  This  form  of  disease  is 
more  common  in  children  than  in  adults  and  is  probably  due  to 
few  bacilli  entering  into  the  circulation. 

PARTIAL  DISSEMINATED  MILIARY  TUBERCULOSIS.  In  this  the 
miliary  tubercles  are  limited  to  certain  organs  or  even  parts  of 
organs.  It  is  often  seen  in  the  lungs  and  is  due  to  a  few  tubercle 
bacilli  entering  the  circulation  and  being  retained  in  the  first 
capillaries  they  encounter.  Occasionally,  in  an  organ  there  is  a 
circumscribed  formation  of  miliary  tubercles  in  an  area  having  the 
form  of  an  infarction.  This  is  due  to  tuberculosis  of  the  artery 
supplying  this  territory  or  the  lodgment  in  it  of  an  embolus  which 
contains  bacilli  but  which  does  not  completely  occlude  the  vessel. 
The  bacilli  are  then  distributed  in  the  area  supplied  by  the  artery. 

LOCAL  TUBERCULOSIS.  In  this  form  the  tuberculosis  tends  to 
remain  limited  to  the  focus  in  which  it  started.  Foci  of  tubercles, 
which  have  become  completely  walled-off,  preventing  further  ex- 
tension, may  be  found  in  any  organ,  but  are  more  common  in 
certain  organs  than  in  others.  In  other  cases  there  is  a  tendency 
to  local  extension,  but  little  or  no  tendency  to  generalization. 
The  best  examples  of  this  are  seen  in  tuberculosis  of  the  skin  and 
bones.  It  is  due  to  the  tissue  not  offering  suitable  conditions  for 
the  rapid  growth  of  the  bacilli  or  to  the  fact  that  the  anatomical 
structure  of  the  part  does  not  offer  favorable  conditions  for 
dissemination. 

TUBERCULOSIS  OF  THE  LUNGS.  In  no  organ  of  the  body  are 
such  constant  and  extensive  lesions  caused  by  tuberculosis,  and 


250  PATHOLOGY 

in  none  are  there  such  opportunities  for  dissemination.  This  is 
due  to  the  extent  of  the  surface  and  the  opportunities  by  means  of 
the  bronchi,  lymphatics  and  blood  vessels  for  the  distribution  of 
bacilli  within  the  organ.  The  bronchi  form  the  main  channel  for 
the  extension  of  infection,  but  not  the  only  one.  Infection  may 
extend  along  the  lymphatics.  The  blood  vessels  are  extremely 
abundant.  Tuberculosis  of  the  larger  vessels  is  not  uncommon 
and  this  must  be  true  also  of  the  smaller  vessels  and  capillaries. 
The  abundance  of  the  exudation  in  the  process  gives  material  in 
which  the  tubercle  bacilli  can  multiply.  The  lesions  caused  by 
tuberculosis  are  further  intensified  by  the  action  of  other  organisms, 
particularly  the  pathogenic  cocci,  which  find  in  the  lesions  pro- 
duced by  the  tubercle  bacilli  favorable  conditions  for  their  own 
action.  In  chronic  tuberculosis  of  the  lung  there  is  an  infinite 
number  of  changes  which  give  a  great  variety  to  the  lesions.  Cer- 
tain processes  can  be  singled  out  and  described  separately,  but  they 
may  all  take  place  together. 

In  marked  cases  of  general  miliary  tuberculosis  of  the  lungs  the 
lungs  do  not  collapse  on  opening  the  chest.  They  are  heavier  than 
normal  and  parts  almost  sink  when  thrown  into  water,  but  air  is 
never  wholly  absent.  They  usually  are  greatly  congested  and  of 
a  dark  red  color.  The  congestion  is  more  pronounced  in  the  lungs 
of  adults  than  in  children.  The  pleural  surface  usually  shows 
grey,  often  transparent,  tubercles.  They  may  be  evenly  distrib- 
uted over  the  surface  or  may  be  more  abundant  in  places.  On 
section  of  the  lungs  the  tubercles  stand  out  from  the  cut  surface 
and  they  may  be  felt  as  small  projecting  points.  They  are  rather 
more  abundant,  particularly  in  children,  in  the  lower  than  in  the 
upper  lobes  of  the  lung.  On  microscopical  examination  the 
tubercles  vary  in  size  and  in  the  extent  of  the  central  caseation. 
The  periphery  usually  is  not  round  because  the  joining  air  spaces 
take  part  in  their  formation  and  become  partly  occluded  by  cells. 
Even  in  the  formation  of  miliary  tubercles  there  may  be  a  con- 
siderable amount  of  exudation  in  which  fibrin  is  present.  Giant 
cells  usually  are  present  and  may  be  formed  from  the  cells  lining 
the  air  spaces,  in  which  free-lying  giant  cells  are  occasionally  found. 
The  tubercles  often  are  in  considerable  numbers  in  the  connective 
tissue,  in  the  walls  of  the  bronchi  and  blood  vessels.  Not  infre- 
quently they  are  found  in  the  interior  of  small  vessels,  projecting 


FORMS  OF  TUBERCULOSIS  251 

from  the  intima.  The  tubercle  bacilli  reach  the  tissue  by  means 
of  the  blood  vessels,  and  the  process  begins  in  the  vascular  endo- 
thelium.  The  occlusion  of  the  blood  vessels,  which  is  so  striking 
on  the  injection  of  the  blood  vessels  of  the  lung,  is  due  to  the 
proliferation  of  endothelium.  Miliary  tubercles  are  constantly 
present  as  a  part  of  all  tuberculous  processes  in  the  lung.  They 
are  often  distributed  around  the  larger  areas  due  to  the  dissemina- 
tion of  the  tubercle  bacilli  by  the  lymphatics.  It  is  not  uncommon 
to  find  large  areas  of  extensive  tuberculous  broncho-pneumonia 
and  around  these  miliary  tubercles  in  such  numbers  that  the 
separate  foci  blend  together.  Conglomerate  tubercles  are  com- 
mon also,  and  in  the  more  chronic  form  of  miliary  tuberculosis  the 
majority  of  the  tubercles  are  conglomerate;  in  each  several  centres 
of  caseation  may  be  recognized.  All  of  the  tuberculous  processes 
may  be  accompanied  by  the  formation  of  diffuse  tuberculous  tissue 
composed  of  epithelioid  and  giant  cells,  more  or  less  exudation 
and  irregular  areas  of  caseation. 

CASEOUS  TUBERCULOUS  PNEUMONIA  is  essentially  a  process  of 
exudation.  The  exudation  varies  in  character.  It  always  con- 
tains a  considerable  amount  of  fibrin  in  which  there  are  numerous 
cellular  elements.  These  cells  are  in  part  due  to  exudation  and  in 
part  to  proliferation  of  the  lining  epithelium.  The  entire  area  of 
the  lung  affected,  both  exudation  and  the  tissue  containing  it, 
undergoes  caseation,  by  which  it  is  converted  into  a  comparatively 
soft,  whitish  gray  mass  which  may  have  a  more  or  less  slaty  color 
from  the  presence  of  pigment.  These  areas  vary  in  size  and  dis- 
tribution. They  may  be  so  small  as  to  simulate  miliary  tubercles, 
or  the  process  may  involve  an  entire  lobe  or  even  an  entire  lung. 
The  larger  areas  may  be  due  to  confluence  of  small  areas  or  to  the 
simultaneous  infection  of  all  parts  of  the  lobe.  The  areas  usually 
are  irregularly  distributed,  one  or  both  lungs  being  affected.  They 
are  more  common  in  the  lower  lobes  than  in  the  upper.  In  the 
caseous  tissues  the  walls  of  the  air  spaces  usually  can  be  recognized. 
In  rare  cases  exudation  may  be  composed  entirely  of  polynuclear 
leucocytes,  the  whole  focus  resembling  an  abscess,  and  in  these 
cases  there  are  immense  numbers  of  tubercle  bacilli  within  the 
leucocytes. 

TUBERCULOUS  BRONCHITIS  AND  PERIBRONCHITIS  occurs  in  case- 
ous pneumonia  because  all  the  bronchi  included  in  the  areas  are 


252  PATHOLOGY 

affected  in  the  same  way  as  the  air  spaces.  In  certain  cases  the 
bronchi  are  affected  chiefly  and  there  is  a  direct  extension  through 
the  wall  into  the  surrounding  lung  tissue.  The  bronchi  may  be 
filled  with  exudate  and  proliferated  cells.  The  epithelium  may  be 
entirely  lost,  or  adhering  masses  of  the  cylindrical  cells  may  be 
mingled  with  the  contents.  Definite  tuberculous  tissue  forms  in 
the  bronchial  wall  and  projects  into  the  lumen.  In  certain  cases 
the  bronchus  seems  to  be  affected  secondarily  to  the  surrounding 
tissue.  The  infection  of  the  bronchus  may  result  not  from  the 
interior  but  from  extension  of  tuberculosis  of  the  peribronchial 
tissue  due  to  lymphatic  infection.  There  may  be  a  considerable 
formation  of  miliary  tubercles  immediately  around  the  bronchi  in 
these  cases.  The  bronchi  may  be  recognized  in  longitudinal  sec- 
tion as  caseous  branching  streaks  or  in  transverse  section  as  solid 
caseous  masses  with  miliary  tubercles  about  them. 

There  is  a  greater  tendency  in  the  lung  than  elsewhere  for  the 
caseous  material  to  undergo  softening.  The  softening  is  some- 
times associated  with  the  presence  of  great  numbers  of  tubercle 
bacilli  and  an  invasion  of  the  caseous  tissue  by  leucocytes.  Cavities 
are  formed  in  consequence  of  softening.  The  presence  of  these 
cavities  and  the  evident  destruction  of  the  tissue  has  given  the 
name  phthisis  to  chronic  ulcerative  tuberculosis  of  the  lung.  The 
cavities  vary  in  form  and  size.  The  softening  may  take  place 
rapidly  in  the  pneumonic  areas  and  a  series  of  irregular  branching 
cavities,  corresponding  to  the  areas  of  pneumonia,  may  be  formed. 
All  of  the  tuberculous  cavities  of  the  lung  open  into  bronchi.  The 
cavities  when  once  formed  can  increase  in  size  by  the  extension  of 
the  tuberculous  process  about  them  and  the  continuation  of  the 
softening.  In  a  large  area  of  tuberculous  pneumonia  there  may 
be  a  simultaneous  formation  of  several  cavities  which  coalesce  by 
extension.  In  other  cases  the  cavity  ceases  to  enlarge,  the  softened 
material  is  discharged  and  dense  cicatricial  tissue  may  form  in  the 
wall.  There  may  be  slow  formation  of  miliary  tubercles  or  of 
tuberculous  tissue  in  the  wall,  with  very  slow  extension  of  the 
caseation,  and  in  still  other  cases  the  cavity  may  be  lined  with  a 
vascular  granulation  tissue  without  tubercles.  In  the  extension 
of  the  softening  and  cavity  formation  there  is  a  difference  in  the 
resistance  of  different  tissues.  The  connective  tissue  cells  of  the 
vessels  are  more  resistant  than  the  intervening  lung  tissue  and  these 


FORMS  OF  TUBERCULOSIS  253 

are  frequently  left  as  bands  traversing  the  cavities  or  projecting 
from  the  walls.  Coincident  with  the  cavity  formation  the  tuber- 
culosis extends.  The  softened  material  contains  numerous  tubercle 
bacilli  which  enter  into  the  bronchi  and  may  be  carried  into  different 
parts  of  the  same  or  both  lungs.  The  walls  of  the  cavities  some- 
times serve  as  breeding  places  for  the  bacilli,  these  growing  on  the 
surface  as  in  pure  culture. 

New  formation  of  connective  tissue,  which  must  be  regarded  as 
reparative  in  character,  constantly  accompanies  the  process.  It 
may  form  such  a  marked  feature  that  the  name  fibroid  phthisis 
may  be  applied.  The  new  formation  of  connective  tissue  produces 
great  thickening  around  the  vessels  and  bronchi  and  bands  of 
connective  tissue  are  given  off  which  traverse  the  lung  and  in  part 
compress  and  in  part  fill  up  the  air  spaces.  In  such  connective 
tissue  the  remains  of  air  spaces  are  seen  as  more  or  less  irregular 
spaces  or  slits  lined  with  a  low  cylindrical  columnar  epithelium, 
the  structure  resembling  glands.  Most  of  the  capillaries  in  the 
walls  are  occluded  and  such  areas  probably  take  but  little  part  in 
respiration.  Changes  in  the  blood  vessels  constantly  accompany 
the  process.  The  large  vessels  in  the  areas  affected  become  oc- 
cluded by  the  formation  of  connective  tissue  within  them.  In  no 
place  can  the  compensatory  endarteritis  which  takes  place  on  the 
diminution  of  a  vascular  territory  be  so  well  seen  as  in  such  lungs. 
A  large  blood  vessel  may  have  its  lumen  many  times  reduced  by 
this  process.  Rupture  of  large  blood  vessels  of  the  lung  from 
weakening  of  their  walls  by  the  destructive  process  is  compara- 
tively rare.  The  small  haemorrhages  which  are  so  common  in  lung 
tuberculosis  are  due  usually  to  rupture  of  small  vessels  or  to  a 
haemorrhagic  exudation.  Thrombi  usually  are  formed  before  the 
large  vessels  are  opened  by  ulceration  or  they  become  occluded  by 
obliterating  endarteritis.  When  a  large  vessel  joins  a  tuberculous 
cavity  a  thrombus  may  form,  or  the  wall  where  weakened  by  the 
extension  of  the  tuberculous  process  may  gradually  give  way,  re- 
sulting in  the  formation  of  an  aneurysm  which  projects  into  the 
cavity.  Severe  and  fatal  haemorrhages  sometimes  result  from  the 
rupture  of  such  aneurysms. 

There  are  other  conditions  in  the  lung  not  due  to  the  tuberculous 
process  in  itself,  but  to  the  conditions  produced  by  the  tuberculosis. 
Atelectasis  may  be  caused  by  the  occlusion  of  bronchi  by  caseous 


254  PATHOLOGY 

masses  either  formed  there  as  an  exudate,  or  brought  from  some 
other  parts  of  the  lung.  The  area  of  lung  supplied  by  the  bronchus 
collapses  because  of  the  absorption  of  the  air.  Emphysema  also 
is  extremely  common,  due  to  expansion  of  the  areas  of  lung  which 
adjoin  the  tuberculous  foci. 

TUBERCULOSIS  OF  Mucous  MEMBRANES.  The  type  of  tuber- 
culosis here  is  the  tuberculous  ulcer.  This  has  much  the  same 
characteristics  wherever  formed.  It  varies  in  size  and  depth,  the 
edges  are  irregular,  often  elevated  and  undermined.  The  base  is 
irregular  and  usually  small  elevated  gray  or  yellowish-white  masses 
(miliary  tubercles)  are  seen  on  and  beneath  the  surface.  The 
ulcers  are  due  to  the  formation  of  tubercles  or  tuberculous  tissue 
beneath  the  epithelium  and  to  the  necrosis  of  the  overlying  surface. 
The  ulcer  extends  laterally  and  in  depth  by  continued  formation 
of  tubercles  and  softening  of  the  caseous  centres.  There  is  a 
continuous  slow  and  irregular  destruction  of  tissue.  In  the  trachea 
the  ulcers  usually  are  small  and  shallow.  They  may  be  confluent 
resulting  in  large  shallow  ulcers  with  a  rough  base  which  may 
cover  the  entire  posterior  wall  of  the  trachea.  In  the  larynx  the 
ulcers  are  smaller,  deeper  and  more  undermined.  Such  ulcers  are 
secondary  to  tuberculosis  of  the  lungs  and  are  produced  by  the 
infection  of  the  surface  by  the  tubercle  bacilli  in  the  sputum.  In 
tuberculosis  of  the  tonsils  the  infection  takes  place  from  the  crypts. 
The  tonsils  undoubtedly  form  a  point  of  entry  for  the  tubercle 
bacilli  in  certain  cases.  The  tubercles  are  formed  in  the  lymphoid 
tissue  surrounding  the  crypts.  Tuberculous  ulcers  are  common 
in  the  alimentary  canal  and  are  found  there  in  their  most  charac- 
teristic form.  In  the  small  intestine  they  have  much  the  same 
distribution  as  the  typhoid  ulcers.  Unlike  these  they  generally 
have  their  greatest  diameter  transverse  to  the  long  axis  of  the 
intestine  due  to  the  process  extending  in  the  course  of  the  lym- 
phatics. They  can  be  distinguished  from  other  forms  of  ulcera- 
tion  by  the  presence  of  miliary  tubercles  in  the  peritoneum  im- 
mediately over  them.  Tuberculosis  of  the  alimentary  canal  is 
almost  always  secondary  to  tuberculosis  of  the  lungs,  the  sputum 
carrying  the  infection;  but  it  may  be  primary,  especially  in  chil- 
dren. Tuberculous  ulcers  in  the  oesophagus,  stomach  and  upper 
fourth  of  the  small  intestine  are  extremely  rare. 

TUBERCULOSIS  OF  THE  GENITAL  SYSTEM  is  rather  more  common 


FORMS  OF  TUBERCULOSIS  255 

in  males  than  in  females.  In  the  male  owing  to  the  intimate  con- 
nection between  the  genital  and  urinary  organs  there  rarely  is 
infection  of  one  system  without  infection  of  the  other.  In  the 
female  there  is  not  the  same  opportunity  for  infection  to  extend 
from  one  set  of  organs  to  the  other.  In  genital  tuberculosis  in  the 
male  the  infection  may  be  primary,  or  secondary  to  a  tuberculous 
process  elsewhere  in  the  body.  The  primary  infection  takes  place 
usually  in  the  epididymis.  There  seems  little  probability  that 
bacilli  can  enter  the  epididymis  from  the  urethra.  The  infection 
is  due  to  a  deposit  in  the  epididymis  of  bacilli  from  some  point  of 
concealed  infection  in  the  same  way  as  infection  of  the  bones 
undoubtedly  takes  place.  The  head  of  the  epididymis  is  the  seat 
of  the  most  extensive  lesions.  The  tail  may  be  slightly  affected 
or  escape.  The  tubercles  and  tuberculous  tissue  are  formed  in 
the  tissue  between  the  tubules  and  large  conglomerate  tubercles 
often  are  found.  The  resulting  caseation  may  be  either  soft  or 
comparatively  firm,  depending  on  the  rapidity  of  the  process  and 
the  character  of  the  tissue  formed.  The  process  may  extend 
from  the  epididymis  into  the  testicle,  but  does  not  occur  primarily 
in  the  testicle.  From  the  epididymis  the  infection  extends  upward 
along  the  vas  deferens  of  the  cord.  This  becomes  swollen,  the 
epithelium  is  destroyed  and  the  lumen  filled  with  caseous  material. 
In  some  cases  tubercles  are  found  in  the  wall,  but  generally  the 
process  is  one  of  exudation  and  formation  of  diffuse  tuberculous 
tissue  with  subsequent  caseation.  The  condition  is  rarely  bilateral. 
The  seminal  vesicles  become  infected  by  extension  from  the  vas 
deferens.  They  become  greatly  swollen  by  the  formation  of 
tuberculous  tissue  in  the  walls  and  by  the  filling  of  the  cavities 
with  soft  caseous  material.  One  or  both  vesicles  may  be  affected, 
the  infection  extending  from  one  to  the  other,  but  they  are  rarely 
affected  to  the  same  degree.  In  these  cases  the  prostate  shows 
usually  a  few  caseous  foci,  but  extensive  tuberculous  lesions  com- 
parable to  those  in  the  epididymis  and  seminal  vesicles  are  rare. 
The  urethra  is  rarely  affected.  Tuberculosis  of  the  Fallopian  tube 
is  more  common  than  tuberculosis  in  any  part  of  the  male  genitalia. 
It  may  be  found  in  combination  with  tuberculosis  of  the  uterus  or 
as  a  primary  infection  and  is  commonly  bilateral.  The  tube  is 
often  greatly  swollen  and  elongated,  the  lumen  is  enlarged  and 
filled  with  caseous  material  and  the  mucous  membrane  is  entirely 


256  PATHOLOGY 

destroyed.  In  minor  degrees  only  a  few  miliary  tubercles  may  be 
found  in  the  mucous  membrane.  In  the  advanced  cases  tubercles 
also  are  seen  on  the  peritoneal  surface.  Tuberculosis  of  the  ovary 
is  extremely  rare.  In  cases  of  tuberculosis  of  the  tubes  and  in 
peritoneal  tuberculosis  tubercles  may  be  found  on  the  surface,  but 
the  tissue  of  the  ovary,  like  the  testicle,  has  a  remarkable  resistance. 
Tuberculosis  of  the  uterus  usually  is  accompanied  by  tuberculosis 
of  the  tubes  though  the  reverse  is  not  true.  It  is  more  common  in 
the  fundus  than  in  the  cervix,  but  the  entire  uterine  canal  may  be 
affected.  The  entire  mucous  membrane  is  lost  and  the  surface 
is  covered  with  opaque  and  caseous  masses,  caseation  extending  a 
variable  distance  into  the  wall  and  preceded  by  an  enormous  forma- 
tion of  lymphoid  tissue.  Miliary  tubercles  are  rare. 

TUBERCULOSIS  OF  THE  URINARY  SYSTEM.  Miliary  tuberculosis 
of  the  kidney  forms  a  part  of  general  miliary  tuberculosis  of  hematog- 
enous  origin.  The  tubercles  are  always  less  numerous  in  the 
kidney  than  hi  the  lung,  liver  and  spleen.  They  may  appear  on 
the  surface  as  small  reddish  areas  of  injection,  with  the  small  gray 
points  of  the  tubercle  hi  the  centre.  They  are  more  numerous  in 
the  cortex  than  in  the  pyramids  and  the  glomeruli  frequently  form 
the  point  of  origin  of  the  tubercles.  They  have  the  general  struc- 
ture of  miliary  tubercles  elsewhere.  Not  infrequently  rows  of 
tubercles  or  longitudinal  areas  of  caseation  resulting  from  their 
coalescence  are  found  and  undoubtedly  are  to  be  attributed  to  the 
extension  of  the  process  by  means  of  the  tubules.  Tuberculous 
pyelonephritis,  is  tuberculosis  of  the  kidney  combined  with  tuber- 
culosis of  the  pelvis  and  calices  and  is  characterized  chiefly  by 
destruction  of  tissue.  Nephro phthisis  the  name  sometimes  given  to 
this  condition  indicates  the  tissue  destruction.  It  appears  in  various , 
degrees  and  is  more  commonly  unilateral  than  bilateral.  In  the 
slightest  degree  it  may  be  confined  to  a  single  calyx  and  its  pyramid 
or  may  involve  the  entire  pelvis,  extending  from  this  to  all  parts 
of  the  kidney.  It  usually  takes  the  form  of  diffuse  tuberculous 
tissue  with  subsequent  caseation  and  softening.  The  pyramids 
may  be  entirely  destroyed,  each  calyx  being  represented  by  a 
tuberculous  cavity  extending  deeply  into  the  tissue  or  the  pelvis 
may  appear  as  a  single  cavity  lined  with  caseous  material  and  the 
kidney  tissue  be  reduced  to  a  thin  shell.  There  has  always  been 
a  great  deal  of  dispute  as  to  the  mode  of  infection  in  these  cases. 


FORMS  OF  TUBERCULOSIS  257 

The  main  process  being  in  the  pelvis  of  the  kidney  and  the  pyramids, 
and  the  frequent  association  of  tuberculosis  of  the  epididymis,  has 
given  rise  to  the  view  that  the  process  usually  is  an  ascending  one. 
There  is  no  difficulty  in  this  conception  of  the  infection.  The 
bacilli  may  extend  from  the  bladder  to  the  ureter,  and  thence  to 
the  pelvis  of  the  kidney  by  diffusion  of  bacilli  in  the  urine.  With 
an  overdistended  bladder  there  is  accumulation  of  urine  in  the 
ureter  and  pelvis  with  the  production  of  fluid  continuity  and  in 
such  fluid  the  bacilli  could  be  distributed  by  the  constant  currents 
which  are  present.  It  is  possible  also  that  the  bacilli  may  extend 
from  lower  down  towards  the  kidney  by  means  of  the  lymphatics 
or  by  the  blood.  The  lymphatic  extension  has  been  demonstrated 
experimentally.  In  certain  cases  this  ascending  infection  must  be 
assumed,  but  it  is  equally  sure  that  the  infection  of  the  kidney  can 
take  place  by  the  blood.  A  few  tubercle  bacilli  may  enter  the 
kidney,  establish  a  focus  of  infection  and  from  this  the  infection  of 
the  calices  and  pyramids  takes  place.  Tuberculosis  of  the  ureter 
usually  is  present  in  this  condition  and  takes  the  ulcerative  form. 
There  may  be  numerous  small  ulcers  scattered  over  the  surface  or 
large  ulcerated  areas  due  to  their  coalescence.  There  is  great 
thickening  of  the  wall  due  to  the  formation  of  tuberculous  tissue 
with  extensive  surface  caseation.  Tuberculosis  of  the  bladder  may 
be  associated  with  tuberculosis  of  the  kidney  and  ureter.  The 
lesions  are  more  pronounced  around  the  ureter  of  the  affected 
kidney.  The  area  of  the  trigonum  is  most  affected  and  the  lesions 
take  the  character  of  shallow  ulcers  with  irregular  edges.  Tubercles 
in  the  mucous  membrane,  without  ulceration,  may  be  found  in  the 
vicinity  of  the  ulcers. 

IN  TUBERCULOSIS  OF  THE  LYMPH  NODES  the  bacilli  enter  by 
means  of  the  lymphatics.  In  cases  of  acute  miliary  tuberculosis 
a  few  tubercles  are  found  in  the  nodes.  They  are  so  prone  to 
infection  by  the  lymphatics  that  in  advanced  tuberculosis  in  any 
part  of  the  body  the  corresponding  lymph  nodes  are  almost  in- 
variably affected.  The  only  exceptions  are  in  that  form  of  tuber- 
culosis of  the  skin  known  as  lupus  and  in  some  cases  of  tuberculosis 
of  bone.  It  frequently  is  primary,  especially  in  the  cervical  nodes, 
the  bacilli  probably  entering  from  the  mucous  membrane  of  the 
mouth  or  tonsils  and  producing  no  lesions  at  the  point  of  entry. 
Tuberculosis  of  the  mesenteric  nodes  also  appears  without  evidence 


258  PATHOLOGY 

of  disease  in  the  intestinal  canal.  Lesions  in  the  nodes  point  to 
infection  by  the  lymphatics,  the  first  appearance  of  the  tuberculous 
tissue  being  in  the  peripheral  lymph  sinuses.  In  certain  cases  a 
network  of  caseous  tissue,  corresponding  in  situation  to  the  sinuses, 
may  be  formed  through  the  node.  Both  the  miliary  form  of 
tuberculosis  and  the  diffuse  form  are  found,  the  latter  being  more 
common.  In  the  miliary  form  the  nodes  are  enlarged,  the  capsule 
thickened,  and  around  the  periphery  and  to  some  extent  in  the 
interior  small  gray  points  with  caseous  centres  are  seen.  Even  in 
these  cases  microscopical  examination  will  show  numbers  of  large, 
pale  cells  hi  the  sinuses  with  more  or  less  ill-defined  caseation.  In 
the  other  form  the  lymph  nodes  are  enlarged,  the  capsule  thickened 
and  filled  with  a  soft  or  comparatively  firm  caseous  mass  in  which 
no  cells  can  be  recognized.  This  condition  is  due  to  a  widespread 
diffuse  caseation  of  the  cells  in  the  lymph  sinuses  and  the  inter- 
vening lymphoid  tissue.  In  some  cases  the  node  may  be  inter- 
sected by  bands  of  newly  formed  connective  tissue.  In  the  capsules 
there  are  miliary  tubercles  or  tuberculous  tissue  with  foci  of  casea- 
tion. The  extension  of  the  infection  may,  for  a  time,  be  blocked 
by  the  lymph  nodes,  but  the  bacilli  may  pass  from  node  to  node 
until  the  nodes  of  a  part  form  large  adherent  pockets.  Nodes  so 
small  that  they  ordinarily  are  not  visible  may  be  converted  into 
large  caseous  masses  several  centimetres  in  diameter.  The  tubercle 
bacilli  may  be  conveyed  along  the  lymphatics  producing  no  change 
in  these,  or  the  vessel  may  be  filled  with  a  mass  composed  of  endo- 
thelial  cells,  giant  cells  and  exudation.  By  the  resulting  caseation 
they  are  converted  into  large  white  cords  with  nodular  swellings. 
Such  vessels  often  are  seen  on  the  peritoneal  surface  of  the  intestine 
over"  tuberculous  ulcers  and  extending  towards  the  mesenteric 
lymph  nodes.  A  process  very  similar  may  take  place  in  the 
thoracic  duct.  The  duct  may  become  greatly  enlarged  and  the 
lumen  occluded,  or  the  tuberculous  mass  in  the  wall  may  project 
as  a  thrombus  into  the  lumen. 

TUBERCULOSIS  OF  SEROUS  SURFACES.  The  infection  may  ex- 
tend from  a  point  of  infection  on  the  surface,  as  an  intestinal  ulcer, 
and  be  haematogenous  in  origin.  In  cases  of  acute  miliary  tuber- 
culosis the  process  is  often  very  extensive  on  the  serous  surfaces 
which  are  covered  with  miliary  tubercles  often  so  small  as  scarcely 
to  be  visible.  In  the  peritoneal  cavity  the  tubercles  usually  are 


FORMS  OF  TUBERCULOSIS  259 

more  numerous  in  the  pelvic  peritoneum,  the  bacilli  being  carried 
to  this  place  by  gravity.  Another  favorite  spot  for  their  formation 
is  on  the  under  surface  of  the  diaphragm,  the  direction  of  the  lymph 
stream  here  favoring  their  presence.  The  formation  of  the  tubercles 
may  be  accompanied  by  an  extensive  serous  exudation  which  may 
be  the  first  clinical  manifestation  of  the  disease.  In  the  other  form 
of  tuberculosis  of  the  serous  cavities  there  is  a  combination  of 
tubercle  formation  with  extensive  fibrinous  exudation  and  organi- 
zation. The  tubercles  are  formed  both  on  the  surface  and  in  the 
newly  formed  connective  tissue.  The  process  takes  place  on  both 
visceral  and  parietal  layers  which  become  adherent,  forming  a  mass 
even  a  centimeter  or  more  in  thickness,  which  shows  on  section 
tubercles,  tuberculous  tissue,  newly  formed  connective  tissue  and 
fibrin  or  hyalin  remains  of  this.  In  the  pericardium  such  tuber- 
culous masses  may  form  a  serious  impediment  to  the  contraction 
of  the  heart.  Lime  salts  may  be  deposited  in  the  caseous  tissue. 
Primary  tuberculosis  of  the  serous  membranes  is  probably  more 
frequent  in  the  peritoneum  than  elsewhere  and  is  more  frequent 
in  females  than  in  males  which  points  to  the  possibility  of  infection 
taking  place  by  means  of  the  Fallopian  tubes  with  or  without 
infection  of  these. 

TUBERCULOSIS  OF  THE  MENINGES.  This  occurs  as  a  part  of 
general  miliary  tuberculosis,  or  it  may  be  secondary  to  a  focal 
tuberculous  process.  It  is  probably  never  primary.  How  the 
infection  takes  place  is  uncertain.  Tubercle  bacilli  may  be  con- 
veyed by  the  blood  or  they  may  enter  by  means  of  the  perineural 
lymphatics,  as  along  the  intercostal  nerves  in  tuberculosis  of  the 
pleura.  The  infection  usually  is  more  marked  in  the  cerebral  than 
in  the  spinal  meninges  though  both  are  affected.  Exudation  plays 
a  very  prominent  part  in  the  process.  In  addition  there  are 
tubercles  and  tuberculous  tissue  which  particularly  affect  the 
adventitia  and  to  a  certain  extent  the  entire  wall  of  the  blood 
vessels.  The  parts  most  affected  are  the  base  of  the  brain,  the 
Sylvian  fissure  and  the  superior  surface  of  the  cerebellum.  The 
dura  is  rarely  affected.  Tuberculosis  of  the  meninges  often  is 
accompanied  by  increased  secretion  in  and  dilatation  of  the  lateral 
ventricles.  Dilatation  of  the  ventricles  may  be  produced  also  by 
the  closure  of  the  valve  of  Vieussens.  Occasionally  tubercles  may 
be  found  extending  a  short  distance  along  the  vessels,  but  there  is 


26o  PATHOLOGY 

never  a  miliary  tuberculosis  of  the  cerebrospinal  tissue.  The  only 
form  in  which  tuberculosis  is  seen  here  is  that  of  circumscribed 
larger  or  smaller  masses  of  tuberculous  tissue  known  as  solitary 
tubercles.  They  are  slow  in  formation  and  are  conglomerate  in 
character,  resulting  from  the  continual  peripheral  formation  of 
miliary  tubercles  around  a  centre  formed  by  the  union  of  the  case- 
ous foci.  They  are  more  common  in  the  cerebellum  than  in  any 
part  of  the  brain  and  are  rare  hi  the  cord.  The  solitary  tubercles, 
particularly  in  the  cerebellum,  often  proceed  from  a  circumscribed 
infection  of  the  meninges.  Great  numbers  of  tubercle  bacilli  may 
be  found  especially  when  the  process  is  chiefly  inflammatory  in 
character.  In  the  solitary  follicles  they  usually  are  extremely  rare. 

TUBERULOSIS  OF  THE  LIVER  is  more  common  than  tuberculosis 
in  any  other  organ  of  the  body,  because  wherever  the  seat  of  in- 
fection a  few  tubercles  usually  will  be  found  in  the  liver.  Infection 
takes  place  by  means  of  the  blood  and  the  extensive  capillary 
circulation  favors  retention  in  the  liver  of  any  tubercle  bacilli  which 
may  enter  the  circulation.  The  form  is  almost  entirely  miliary 
although  large  solitary  tubercles  have  been  described.  The 
miliary  tubercles  are  situated  in  the  periphery  of  the  lobules,  they 
never  attain  a  large  size  and  a  very  few  bacilli  are  found  in  them. 
The  tubercles  always  are  larger  in  miliary  tuberculosis  of  children 
than  they  are  in  the  adult.  Another  form  of  liver  tuberculosis 
is  that  of  the  bile  ducts.  In  this  the  infection  extends  along  the 
lymphatics  of  the  bile  ducts  leading  to  formation  of  diffuse  tuber- 
culous tissue  in  the  wall,  destruction  of  epithelium  and  caseation, 
the  caseous  mass  being  stained  with  bile.  Sections  show  a  softened, 
bile-stained  caseous  mass  in  the  centre,  and  surrounding  this  a  wall 
of  tuberculous  tissue  with  advancing  caseation. 

TUBERCULOSIS  OF  THE  BONES  AND  JOINTS.  This  may  be  secon- 
dary to  tuberculous  diseases  elsewhere  in  the  body,  but  in  certain 
cases  is  primary.  In  the  long  bones  tuberculosis  begins  almost 
invariably  in  the  marrow  of  the  epiphysis.  The  process  does  not 
really  differ  from  tuberculosis  in  other  tissues.  By  coalescence  and 
caseation  the  marrow  may  be  destroyed  over  considerable  areas. 
Definite  tuberculous  cavities  in  the  bone  can  be  formed,  the  trabec- 
ulae  of  the  bone  being  entirely  or  partly  dissolved  in  the  process 
of  softening.  The  process  has  many  analogies  with  suppurative 
osteomyelitis,  but  is  never  so  extensive.  The  most  common  situa- 


FORMS  OF  TUBERCULOSIS  261 

tion  for  tuberculosis  of  the  bones  is  in  the  bodies  of  the  vertebrae. 
The  disease  begins  usually  near  the  articulating  surface  at  the 
anterior  portion  of  the  body.  The  intervertebral  substance  is 
destroyed  and  the  infection  extends  to  the  adjacent  vertebrae.  In 
consequence  of  such  destruction  of  the  bodies  of  the  vertebrae  the 
vertebral  column  gives  way  to  the  pressure  forming  a  knuckle  at 
the  point  of  disease.  The  infection  may  extend  to  the  soft  parts 
producing  a  tuberculous  abscess.  Infection  of  the  joints  always 
is  secondary  to  tuberculosis  of  the  bones.  The  entire  synovial 
surface  of  the  joint  may  become  infected  resulting  in  the  formation 
of  tuberculous  tissue  and  exudation. 

TUBERCULOSIS  or  THE  SKIN  occurs  in  a  variety  of  forms  affecting 
the  different  tissues.  The  most  common  form  is  the  anatomical 
tubercle.  This  is  an  infection  of  Jthe  skin  from  the  surface,  which 
occurs  on  the  hands  of  those  who  come  in  contact  with  tuberculous 
material.  It  consists  of  a  circumscribed  hypertrophy  of  the  epi- 
dermis and  of  the  papillary  layer  with  great  thickening  of  the 
papillae  so  as  to  produce  a  wart-like  swelling.  Sections  show  a 
tissue  composed  of  endothelial  cells  with  slight  tendency  to  casea- 
tion  and  very  few  tubercle  bacilli.  The  process  is  extremely 
chronic  and  there  is  little  tendency  for  the  infection  to  extend. 
The  second  form  is  lupus.  In  this  there  is  a  formation  of  miliary 
tubercles  and  of  tuberculous  tissue  in  the  corium.  It  is  associated 
with  a  marked  new  formation  of  connective  tissue  and  has  a  slight 
tendency  to  surface  ulceration.  It  is  exceedingly  chronic,  it  tends 
to  persist  and  to  extend  very  slowly.  A  very  few  tubercle  bacilli 
are  found  hi  association  with  the  lesions.  The  third  form  is  the 
tuberculous  ulcer  of  the  skin  which  does  not  differ  from  tuberculous 
ulcers  in  the  mucous  membranes.  The  process  is  seated  in  the 
subcutaneous  tissue;  there  is  undermining  of  theedges  of  the 
ulcers  and  the  formation  of  tuberculous  tissue  at  the  base.  In 
cases  of  acute  miliary  tuberculosis  in  children  there  often  is 
a  peculiar  eruption  of  the  skin  associated  with  the  process.  This 
appears  as  small  areas  of  hyperemia  surrounding  slight  papillary 
elevations.  In  other  cases  in  the  centre  of  the  areas  of  hyperemia 
there  may  be  a  formation  of  small  vesicles  or  small  crusts  due 
to  drying  of  the  surface.  On  microscopical  examination  hi  these 
areas  there  is  no  characteristic  tissue  reaction.  Usually  a  slight 
infiltration  with  lymphoid  and  endothelial  cells  with  an  occasional 


262  PATHOLOGY 

giant  cell  is  found.  There  is  little  or  no  tendency  to  caseation. 
In  other  cases  there  appears  to  be  nothing  more  than  a  slight  serous 
exudation.  Tubercle  bacilli  are  found  in  varying  numbers  and 
may  be  in  the  tissue  in  considerable  numbers  without  tissue  reac- 
tion about  them.  Tuberculosis  of  the  skin  has  an  especial  place 
in  the  history  of  the  disease  owing  to  the  fact  that  lesions  here  have 
but  slight  tendency  to  extend.  The  skin  must  be  regarded  as  a 
tissue  of  very  great  resistance.  Owing  to  the  extent  of  the  sur- 
face, tubercle  bacilli  must  in  most  cases  be  brought  to  the  skin  and 
yet  tuberculous  lesions  are  rare. 

A  CASE  OF  CHRONIC  PULMONARY  TUBERCULOSIS  WITH 
TUBERCULOUS  MENINGITIS 

Anatomical  Diagnoses.  Tuberculosis  of  lung  with  cavity  formation, 
discrete  and  conglomerate  tubercles,  and  tuberculous  pneumonia; 
Tuberculous  pleurisy;  Tuberculosis  of  vermiform  appendix; 
Tuberculous  meningitis. 

White,  male,  age  eighteen  years.  Body  well  developed,  fairly  well 
nourished.  No  rigor  mortis,  body  still  warm.  Slight  post-mortem 
lividity  of  dependent  portions.  No  oedema.  Pupils  are  unequal. 
Subcutaneous  fat  yellow,  1.5  cm.  in  thickness.  Muscles  red. 

Peritoneum  smooth.  Intestines  somewhat  distended  with  gas.  The 
appendix  9  cm.  in  length,  is  uniformly  thickened,  its  distal  end  clubbed 
and  reddened.  It  is  adherent  throughout  to  the  peritoneum  lining  the 
ileo  caecal  fossa. 

The  left  lung  is  adherent  at  apex  by  firm  fibrous  adhesions.  The  right 
pleural  cavity  is  completely  obliterated.  Pericardium  and  heart  normal. 
Coronary  arteries  and  aorta  normal. 

Throughout  the  upper  lobe  of  the  left  lung  there  are  small  discrete, 
conglomerate,  tubercles,  yellow  in  color,  and  slightly  raised  above  the 
surrounding  lung  tissue.  These  tubercles  are  more  prominent  and  more 
numerous  in  the  lower  margin  of  this  lobe.  In  the  lower  lobe  there  are 
similar  tubercles,  but  less  numerous,  and  the  lung  tissue  between  the  foci 
is  somewhat  congested.  On  the  pleural  surface  of  the  right  lung  there 
are  numerous  tubercles.  The  lung  is  firm  and  noncrepitant  except  for 
a  small  area  of  tissue  in  the  posterior  and  lateral  aspect  of  the  lower  lobe. 
Throughout  all  lobes  there  are  numbers  of  conglomerate  tubercles  up  to 
i  cm.  in  diameter.  In  other  areas  in  the  lung  there  are  solid,  firm, 
completely  caseated  areas  of  tuberculous  pneumonia.  Throughout  the 
upper  and  middle  lobes  are  numerous  cavities  with  rough,  caseous  walls 


FORMS  OF  TUBERCULOSIS  263 

connecting  with  the  bronchi.  The  largest  of  these  cavities  is  in  the 
central  portion  of  the  middle  lobe. 

Spleen  firm,  weight  225  grams.    Follicles  prominent. 

Liver,  weight,  1750  grams.    Dark  red  and  firm,  lobules  evident. 

Kidneys,  combined  weight,  360  grams.    Surface  smooth,  dark  red. 

The  gastro-intestinal  tract  with  the  exception  of  appendix  is  normal. 
The  lumen  of  appendix  is  somewhat  dilated,  and  at  the  distal  end  there 
is  a  small  ulcer  which  extends  into  a  softened  tuberculous  mass  which 
infiltrates  the  wall.  The  peritoneum  over  this  is  injected,  but  otherwise 
normal.  Adrenals  normal. 

Brain.  Along  the  vessels  of  the  pia  on  the  lateral  aspect  of  the  brain 
a  few  small  grayish  nodules  can  be  seen.  Along  the  vessels  of  the  Sylvian 
fissure  on  both  sides  these  nodules  are  very  much  more  numerous,  the 
vessels  in  places  apparently  converted  into  caseous  cords.  The  whole 
tissue  of  the  pia-arachnoid  here  is  thickened  and  firmly  adherent.  At 
the  base  of  the  brain  between  the  crura,  over  the  lower  surface  of  the 
cerebellum  and  extending  to  the  upper  surface,  are  numerous  tubercles 
along  the  vessels  and  a  considerable  amount  of  caseous  exudation. 
Both  lateral  ventricles  are  dilated  and  contain  an  increased  amount  of 
slightly  turbid  fluid.  Over  the  surface  of  the  fourth  ventricle  there  are 
numerous  prominent  ependymal  granules. 

Microscopic  examination  of  the  tissue  in  this  case  shows  in  the  sections 
of  the  brain  an  extensive  tuberculosis  of  meninges  and  vessels  which  at 
various  points  extend  into  the  cerebral  cortex.  Where  the  exudation 
is  best  marked  there  is  increase  in  the  cortical  neuroglia. 

REMARKS.  The  tuberculous  meningitis  in  this  case  is  extensive 
and  is  accompanied  by  an  unusual  degree  of  cortical  gliosis.  The 
tuberculosis  of  the  lungs  is  evidently  the  oldest  focus.  An  unusual 
feature  of  the  case  is  the  tuberculosis  of  the  vermiform  appendix. 
Infection  here  resulted  from  the  tubercle  bacilli  in  the  alimentary 
canal  which  were  contained  in  the  sputum.  The  infrequency  of 
tuberculosis  of  the  vermiform  appendix  is  rather  remarkable  in 
view  of  the  possibility  for  infection  which  this  would  seem  to  offer. 

A  CASE  OF  ACUTE  GENERAL  MILIARY  TUBERCULOSIS 

FOLLOWING  TUBERCULOSIS  OF  THORACIC  DUCT. 

EMPHYSEMA  OF  CHEST 

Anatomical  Diagnoses.  Tuberculous  ulcers  of  intestine;  Tuber- 
culosis of  mesentery  glands;  Tuberculosis  of  thoracic  duct; 
General  miliary  tuberculosis;  Subcutaneous  emphysema;  Strep- 
tococcus septicaemia;  Pneumothorax. 


264  PATHOLOGY 

White,  male,  age  twenty-three  years.  The  body  large,  fairly  well 
nourished.  There  is  subcutaneous  emphysema  over  the  entire 
thorax  and  neck.  The  subcutaneous  fat  of  medium  amount,  muscles 
pale. 

In  the  peritoneal  cavity  a  slight  increase  in  the  amount  of  fluid.  In 
the  mid-clavicular  line  the  liver  is  depressed  4  cm.  below  the  costal 
margin.  Diaphragm  on  right  side  at  sixth  rib,  on  left  at  fourth. 

On  opening  the  chest  there  is  an  escape  of  gas  from  the  right  pleura! 
cavity.  The  tissue  of  the  mediastinum  is  infiltrated  with  gas.  The 
pericardial  tissue  also  contains  gas,  but  there  is  none  in  the  pericardial 
cavity.  There  is  considerable  gas  beneath  the  pleura  around  the  hilum 
of  the  right  lung.  A  small  amount  in  similar  position  in  left  lung. 
There  is  no  air  beneath  the  parietal  pleura. 

Both  lungs  are  free  from  adhesions.  In  the  bronchi  there  is  a  large 
amount  of  muco-purulent  secretion.  Throughout  both  lungs  the  tissue 
is  studded  with  very  fine  miliary  tubercles,  homogeneously  distributed. 
Considerable  air  is  contained  in  the  interstitial  tissue  of  the  left  lung  and 
a  small  amount  is  beneath  the  pleura  of  the  right  lung.  The  tubercles 
appear  as  circumscribed,  pearly  gray  nodules  up  to  i  mm.  in  diameter. 
There  are  no  conglomerate  tubercles,  no  caseous  pneumonia,  no  evidence 
of  an  older  tuberculous  process.  The  bronchial  lymph  nodes  are  en- 
larged and  contain  in  their  interior  and  in  their  capsules  small,  scarcely 
visible  miliary  tubercles. 

The  heart  is  of  medium  size,  the  valves  and  myocardium  normal. 
No  gas  in  the  vessels  of  the  body. 

The  liver  is  pale,  slightly  enlarged.  Scattered  tubercles  are  visible 
on  the  surface  and  on  section. 

The  spleen  is  enlarged,  the  capsule  tense,  the  tissue  comparatively 
soft.  Innumerable  miliary  tubercles,  the  largest  i  mm.  in  diameter,  are 
scattered  throughout  the  tissue. 

The  kidneys  are  enlarged.  On  the  surface  are  numerous  small  pale 
tubercles  with  vascular  injection  of  the  surrounding  tissue.  On  section 
scattered  tubercles  are  found. 

Gastro-intestinal  canal.  Stomach  normal.  About  i  mm.  above  the 
ileo-ccecal  valve  there  is  an  ulcer  with  irregular  nonelevated  edges.  In 
the  base  and  at  the  edge  of  the  ulcer  there  are  numerous  small  points 
of  caseation.  Adjoining  this  larger  ulcer  there  is  a  small  ulcer  of  the  same 
character.  In  the  vicinity  of  the  valve  there  are  several  small  and 
comparatively  fresh  ulcers.  Through  the  peritoneal  surface  over  these 
ulcers  there  are  numerous  fine  sub-peritoneal  miliary  tubercles.  A  few 
tubercles  are  found  on  the  surface  of  the  pelvic  peritoneum  in  Douglas's 
cul-de-sac. 


FORMS  OF  TUBERCULOSIS  265 

The  lymph  nodes  in  the  mesentery  are  enlarged,  particularly  those  in 
the  immediate  vicinity  of  the  caecum.  On  section  distinct  caseous  foci 
are  found  within  them.  The  thoracic  duct  in  its  entire  course  through 
the  thorax  is  dilated  and  filled  with  a  thin,  slightly  turbid  fluid.  The 
upper  portion  is  enlarged  to  three  tunes  its  normal  size  and  is  solid. 
The  opening  into  the  subclavian  vein  could  not  be  traced.  On  opening 
the  duct  small  tubercles  were  found  at  various  places  on  the  internal 
surface.  The  upper  portion  of  the  duct  for  a  distance  of  6  cm.  is  lined 
with  caseous  material.  In  most  part  the  surface  of  this  is  smooth  and 
the  duct  has  a  complete  though  irregular  lumen.  In  the  upper  part 
the  material  filling  the  duct  is  softened. 

Brain  and  meninges  injected,  but  no  tubercles  are  found  along  the 
course  of  the  vessels. 

Coverslip  preparations  from  the  fluid  hi  the  thoracic  duct  stained 
for  tubercle  bacilli  were  positive.  Microscopical  sections  of  the  duct 
showed  tubercles  in  the  wall  and  within  the  duct  caseous  material  con- 
taining numbers  of  tubercle  bacilli  in  clumps. 

Sections  of  the  organs  gave  the  usual  picture  of  miliary  tuberculosis. 
Pure  and  abundant  cultures  of  streptococci  were  obtained  from 
heart's  blood,  spleen,  liver,  kidney  and  emphysematous  tissue  in 
mediastinum. 

REMARKS.  In  this  case  the  subcutaneous  emphysema  is  evi- 
dently due  to  the  rupture  of  the  left  lung  near  the  hylum  allowing 
the  air  to  enter  into  the  tissue.  From  here  it  made  its  way  into  the 
mediastinum  and  the  subcutaneous  tissue.  It  is  not  improbable 
that  the  streptococcus  infection  originated  in  this  way.  The  main 
interest  in  the  case  centres  in  the  tuberculosis  of  the  thoracic  duct 
and  the  relation  of  this  to  the  general  miliary  tuberculosis.  The 
infection  must  be  assumed  to  have  been  primary  in  the  intestines. 
The  intestinal  ulcers  represent  the  only  chronic  tuberculous  process 
in  the  body,  and  the  tuberculosis  of  the  mesenteric  lymph  nodes 
followed  the  intestinal  lesion.  The  evident  age  of  the  ulcers  and 
the  infrequency  of  intestinal  ulceration  of  haematogenous  origin  is 
evidence  that  they  are  not  due  to  the  same  source  of  infection 
as  the  miliary  tubercles.  Histologically,  the  lesions  in  the  upper 
portion  of  the  thoracic  duct  consist  chiefly  in  exudation  with  casea- 
tion,  and  followed  an  extensive  tuberculosis  of  the  wall.  In  the 
masses  thus  formed  tubercle  bacilli  have  grown  and  from  here  have 
entered  the  circulation. 


266  PATHOLOGY 

A  CASE  OF  CHRONIC  GENITO-URINARY  TUBERCULOSIS 
WITH  MILIARY  TUBERCULOSIS 

Anatomical  Diagnosis.  Chronic  genito-urinary  tuberculosis; 
Chronic  tuberculosis  of  right  pleurae;  Chronic  fibrous  pleuritis; 
Acute  general  miliary  tuberculosis. 

Male,  white,  age  thirty-seven  years.  The  body  of  medium  size, 
strongly  built,  fairly  well  nourished.  Surface  smooth,  no  oedema. 
Rigor  mortis  marked.  Slight  post-mortem  congestion.  Subcutaneous 
fat  in  medium  amount,  muscles  red. 

Peritoneum  smooth.    The  mucous  membrane  of  pharynx,  larynx  and  • 
trachea  congested.    Heart  weighs  310  grams.    Pericardium  normal. 
Valves  and  myocardium  normal. 

Mucous  membrane  and  bronchi  strongly  congested.  Both  lungs  are 
adherent  to  pleura.  On  the  left  side  just  above  the  diaphragm,  where 
the  lung  is  densely  adherent,  the  pleura  is  greatly  thickened  with  caseous 
material  between  the  layers.  Both  lungs  everywhere  contain  miliary 
tubercles,  homogeneously  distributed.  At  various  places  in  the  left 
lung  close  beneath  the  pleura  there  are  areas  of  recent  haemorrhage 
extending  a  short  distance  into  the  pulmonary  tissue.  In  the  right  lung 
at  the  lower  border  there  is  an  area  of  caseation  which  has  the  general 
configuration  of  an  infarct.  Along  the  upper  edge  of  the  lower  lobe  there 
is  a  similar  dry  caseous  area,  triangular  in  shape.  All  the  blood  vessels 
of  the  lung  opened,  and  in  neither  arteries  nor  veins  are  any  tubercles 
found. 

The  liver  weighs  1620  grams.  Rather  pale.  On  the  surface  and  on 
section  miliary  tubercles  can  be  discerned. 

The  spleen  weighs  265  grams.  The  capsule  wrinkled.  On  section 
filled  with  miliary  tubercles. 

The  capsule  of  the  left  kidney  easily  strips  off.  Throughout  this 
kidney  both  in  the  cortex  and  pyramids  there  are  numerous  large  tubercles, 
many  of  them  apparently  conglomerate,  others  single.  The  pelvis  of 
the  kidney  and  ureter  smooth.  The  right  kidney  is  small,  weight  no 
grams.  The  capsule  adherent.  On  section,  in  places,  the  entire  py- 
ramidal portion  of  kidney  is  destroyed  and  the  calices  converted  into 
tuberculous  sacs,  which  extend  to  within  a  few  millimeters  of  the  surface. 
In  other  places  the  pyramids  are  converted 'into  a  soft,  easily  broken- 
down  caseous  tuberculous  mass.  The  pelvis  is  thickened,  the  surface 
caseous.  The  right  ureter  for  its  entire  distance  shows  the  same  change 
as  the  pelvis,  being  covered  everywhere  with  caseous  tissue  in  and  be- 
neath which  are  miliary  tubercles.  In  the  bladder  around  the  entrance 
of  the  ureter  there  is  an  extensive  surface  loss  of  tissue  and  at  the  bases 


FORMS  OF  TUBERCULOSIS  267 

of  these  erosions  there  are  innumerable  small  projecting  miliary 
tubercles. 

On  both  sides  the  epididymes  are  enlarged,  and  indurated  and  contain 
large,  firm,  caseous  areas.  This  condition  is  more  marked  on  the  right 
than  on  the  left  side.  This  caseation  on  the  right  side  extends  into  the 
tissue  of  the  spermatic  cord,  the  vasa  defferentia  being  converted  into 
a  hard  caseous  fibre  throughout  the  entire  length  of  the  cord.  The 
seminal  vesicles  on  both  sides  are  tuberculous.  On  the  right  it  is  enlarged 
and  solidified,  the  lumen  being  filled  with  caseous  material.  The  mucous 
membrane  of  the  stomach  and  intestines  normal.  Pancreas  and  adrenals 
normal.  All  of  the  lymph  glands  are  enlarged  and  contain  miliary  tuber- 
cles. Examination  of  the  thoracic  duct  negative. 

Aorta  smooth  with  the  exception  of  a  few  scattered  miliary  tubercles 
along  the  intima. 

REMARKS.  In  this  case  it  is  difficult  to  ascertain  the  seat  of  the 
primary  infection.  The  tuberculosis  of  the  genito-urinary  system 
is  apparently  the  oldest  focus  in  the  body  although  the  large  caseous 
area  of  the  right  pleura  is  also  old.  It  is  impossible  to  say  whether 
the  genito-urinary  tuberculosis  was  an  ascending  or  descending 
infection.  From  some  one  of  the  chronic  lesions  the  tubercle 
bacilli  have  gained  entrance  into  the  blood,  this  resulting  in  the 
widespread  miliary  tuberculosis.  In  many  such  cases  it  is  possible 
to  trace  the  point  at  which  the  tubercle  bacilli  gain  entrance  into 
the  blood,  but  in  this  case  it  was  not  possible. 

A  CASE  OF  TUBERCULOUS  PHTHISIS  WITH  AMYLOID  DE- 
GENERATION or  ISLANDS  OF  LANGERHANS  AND 
DIABETES  MELLITUS 

Anatomical  Diagnoses.  Diabetes  mellitus;  Glycogenic  degenera- 
tion of  tubules  of  Henly;  Tuberculosis  of  lung  with  cavity  for- 
mation; Miliary  and  conglomerate  tubercles  in  lung;  Caseous 
tuberculous  pneumonia;  Chronic  fibrous  pleuritis;  General 
arterio-sclerosis;  General  amyloid  degeneration;  Granular  epen- 
dymitis. 

Male,  white,  age  forty-three. years.  Body  well  developed,  poorly 
nourished,  rigor  mortis  present.  Slight  livores  mortis.  No  oedema. 
Subcutaneous  fat  small  in  amount,  muscles  dark  red.  Peritoneum 
smooth,  no  exudation.  Diaphragm  at  fifth  rib  on  right  side,  at  the 
lower  border  of  the  fourth  rib  on  the  left.  Both  pleural  cavities  com- 
pletely obliterated  by  firm  adhesions. 


268  PATHOLOGY 

Pericardial  cavity  negative.  Heart  weight  350  grams.  Myocardium 
normal.  Along  the  coronary  arteries  there  are  small,  white,  circumscribed 
areas  of  sclerosis.  On  sections  of  the  artery  through  such  an  area,  the 
sclerosis  is  lateral  only,  and  the  artery  at  the  point  slightly  narrowed. 
Lungs.  Each  apex  is  occupied  by  a  cavity  into  which  several  bronchi 
open.  The  cavity  at  the  apex  of  the  right  lung  is  4-5  cm.  in  diameter 
and  contains  opaque,  yellow,  tenacious,  necrotic  masses  attached  to  the 
wall.  The  wall  of  the  cavity  extends  irregularly  into  the  surrounding 
lung  tissue,  which  is  for  the  most  part  solid  and  caseous.  The  necrotic 
tissue  of  the  wall  is  bathed  in  gray,  thin,  gruel-like  fluid  containing 
yellowish  specks,  which,  on  examination,  are  composed  of  masses  of 
tubercle  bacilli.  The  cavity  in  left  lung  occupies  the  upper  and  outer 
half  of  the  upper  lobe.  In  places  the  outer  wall  is  1-3  mm.  in  thickness 
and  consists  of  the  thickened  pleura  lined  on  the  inside  with  granulation 
tissue.  Large  masses  of  soft,  opaque,  yellow,  necrotic  tissue  are  attached 
to  the  wall.  The  surface  beneath  pleura  shows  numerous  depressions 
with  necrotic  caseous  tissue  between.  Contents  of  the  cavity  same  as  in 
left  lung.  In  each  upper  lobe  the  tissue  about  the  cavity  is  in  part 
distinctly  caseous,  in  part  tough,  resistant,  and  of  a  slaty  color.  Em- 
bedded hi  this  are  many  firm,  gray  or  yellowish-gray  nodules  (tubercles) 
1-5  mm.  in  diameter,  the  larger  suggesting  a  conglomerate  composition. 
Disseminated  through  the  middle  and  lower  lobes  of  the  right  lung  and 
sparsely  scattered  in  the  lower  lobe  of  the  left  are  a  few  fine,  pearly 
tubercles  and  firm  conglomerate  tubercles  2-5  mm.  in  diameter.  Peri- 
bronchial  lymph  nodes  are  enlarged  and  caseous. 

Spleen  weight  200  grams.  Capsule  thin,  slightly  wrinkled.  Organ 
lax  and  soft.  Malpighian  bodies  small.  Pulp  is  pale  red.  The  tra- 
beculae  are  visible. 

Liver,  weight  1690  grams.  Lobules  visible,  centres  often  slightly 
injected. 

Gall  bladder  and  ducts  normal. 
Pancreas  normal. 

Kidneys,  weight  440  grams.  Capsule  easily  stripped  from  a  smooth 
gray  surface  of  a  yellow  tint.  The  cortex  on  section  pale  and  opaque, 
varying  from  1-0.3  cm-  thickness.  Glomeruli  not  visible.  Pyramids 
pale,  contrasting  slightly  with  cortex. 

The  aorta  shows  a  few  yellowish-gray  elevated  placques  1-4  cm.  in 
diameter.  Behind  the  aortic  cusps  is  a  circular  yellowish  zone  of  sclerosis 
i  cm.  wide;  the  intima  over  all  these  areas  is  smooth. 

The  weight  of  brain  1540  grams.  The  meninges  normal.  Over  the 
floor  of  the  fourth  ventricle  there  are  a  number  of  minute  gray  elevations 
so  close  together  as  to  give  a  fine  roughening  of  the  surface. 


FORMS  OF  TUBERCULOSIS  269 

Middle  ears  normal. 

Microscopical  examination  of  pancreas  shows  amyloid  infiltration  of 
the  walls  of  the  smaller  arteries  and  extending  from  here  to  some  extent 
into  the  surrounding  tissue.  The  amyloid  is  chiefly  marked  in  the 
Islands  of  Langerhans  which  are,  for  the  most  part,  converted  into 
amyloid  masses.  The  kidneys  show  marked  amyloid  of  glomeruli,  of 
glomerular  arteries  and  of  the  straight  vessels  of  the  pyramids.  The 
epithelium  of  the  proximal  convoluted  tubules  is  swollen  and  contains 
hyalin  globules.  The  epithelium  of  Henly's  loops  is  greatly  swollen 
and  vacuolated.  Iodine  staining  after  hardening  in  absolute  alcohol 
shows  in  these  apparent  vacuoles,  hyalin  masses'  (glycogen)  staining 
with  iodine. 

REMARKS.  A  case  of  chronic  tuberculosis  of  lungs  with  resulting 
amyloid.  Amyloid  degeneration  of  Islands  of  Langerhans  result- 
ing in  diabetes,  has  been  followed  by  rapid  extension  of  the  tuber- 
culosis in  the  lung;  this  is  shown  by  the  extensive  necrosis  and 
caseation  and  softening,  large  masses  of  caseous  necrotic  lung  tissue 
being  still  adherent  to  the  wall  of  the  cavity.  It  is  very  probable 
that  in  this  case  the  extension  of  the  process  in  the  lung  was  assisted 
by  a  mixed  infection  with  the  pyogenic  cocci.  In  diabetes,  infec- 
tion is  facilitated  and  infectious  processes  of  all  sorts  extend  more 
rapidly. 


LEPROSY   BACILLUS. 

This  is  a  slender,  often  slightly  curved  bacillus,  presenting  much 
similarity  both  in  morphology  and  in  staining  reaction  to  the 
tubercle  bacillus.  It  can  be  isolated  and  grown  on  special  culture 
media  and  after  several  generations  it  grows  on  ordinary  media. 
The  organism  is  pathogenic  for  Japanese  waltzing  mice  and  for 
monkeys,  in  which  it  produces  fairly  characteristic  nodular  lesions. 

In  man  the  disease  appears  in  two  well-marked  forms,  the  nodular 
or  tubercular  and  the  anaesthetic.  In  the  nodular  form  large  and 
small  circumscribed  nodules  appear  in  the  subcutaneous  tissue, 
preferably  on  the  forehead.  The  nodules  are  in  the  corium,  the 
fibres  of  which  are  separated  by  masses  of  endothelial  cells  which 
appear  in  two  forms,  as  large  cells  resembling  large  phagocytic  cells 
and  as  large  vacuolated  masses.  The  vacuoles  in  these  cells  are 
filled  with  fat.  In  both  sorts  of  cells  there  are  great  numbers  of 
leprosy  bacilli  which  in  the  vacuolated  cells  surround  the  vacuoles. 
There  also  are  large  globular  masses  which  by  some  are  regarded 
as  cells,  by  others  as  thrombosed  lymphatics  which  are  filled  with 
bacilli.  Lesions  very  similar  to  those  of  the  skin,  but  associated 
with  ulceration,  may  be  found  in  the  mucous  membrane  of  the  nose. 
The  lymph  nodes  "are  but  little  enlarged  and  the  sinuses  contain 
numbers  of  the  large  vacuolated  cells  filled  with  bacilli.  Similar 
cells  may  be  found  in  the  liver  and  spleen.  The  source  of  the  fat 
in  these  cells  is  uncertain,  since  the  bacilli  themselves  produce  a 
fatty  substance  which  stains  with  osmic  acid. 

In  the  anaesthetic  form  of  leprosy  there  are  lesions  in  the  nerves 
and  spinal  cord.  The  nerves,  the  interstitial  tissue  and  even  the 
ganglion  cells  of  the  cord  may  contain  great  numbers  of  bacilli. 
Neither  caseation  nor  necrosis  is  associated  with  the  action  of  the 
leprosy  bacilli  in  the  human  body  and  they  produce  little  or  no 
inflammatory  reaction  in  the  tissue  about  them.  The  organism 
must  be  regarded  as  one  with  very  little  virulence  but  with  great 
power  of  proliferation.  Secondary  infection,  especially  with  tuber- 
culosis, is  a  frequent  cause  of  death. 

270 


TREPONEMA  PALLIDUM. 

This  is  a  thin,  threadlike  organism  of  corkscrew  shape,  vary- 
ing in  length  from  4-14  n.  The  curves  are  acute,  symmetrical,  and, 
according  to  the  length  of  the  organisms,  vary  in  number  from  4  to 
20.  The  organism  is  actively  motile  and  may  be  demonstrated  by 
various  methods  of  staining,  the  best  being  by  silver  impregnation. 

OCCURRENCE  OF  ORGANISMS.  The  organisms  are  found,  often 
in  great  numbers,  in  all  the  acute  lesions  of  syphilis  and  in  no  other 
disease.  In  anthropoid  apes  lesions  of  the  same  character  as  the 
human  disease  and  containing  the  treponemata  are  produced  by 
inoculation  with  disease  products  containing  the  organisms.  In 
the  lower  apes  the  primary  lesions  without  secondary  are  produced 
and,  to  a  certain  extent,  infections  are  produced  in  rabbits.  Under 
natural  conditions,  the  disease  is  exclusively  one  of  man.  The 
relation  of  the  organism  to  the  disease  is  further  shown  by  the 
fact  that  infections  by  pure  cultures  have  produced  the  disease  in 
monkeys  and  by  the  immunological  reactions. 

PERIODS  OF  DISEASE.  The  pathology  of  the  disease  can  be 
divided  into  three  periods  which  are  separated  from  one  another 
by  varying  intervals  of  time;  in  different  cases  the  lesions,  in 
location  and  character,  vary  with  the  periods,  but  show  a  general 
interrelation.  The  primary  infection  is  most  frequent  on  the  skin 
of  the  genitalia;  it  is  rare  in  other  places,  and  its  occurrence  is 
favored  by  a  surface  lesion.  At  this  point  there  is  formed,  slowly 
and  without  pain,  a  hard  papule  which  slowly  increases  in  size; 
this  becomes  a  shallow  ulcer  which  produces  a  small  amount  of  thin 
exudate.  In  certain  cases  the  ulcer  is  preceded  by  a  vesicle.  The 
extreme  induration  and  the  circumscribed  character  of  the  lesions 
are  the  most  prominent  features.  Microscopically,  there  is  an 
intense  diffuse  infiltration,  chiefly  with  lymphoid  cells  below  the 
surface,  and  lower  down  the  infiltration  is  localized  around  the 
vessels.  Between  these  foci  of  cell  infiltration  there  is  prolifera- 
tion of  the  connective  tissue.  The  walls  of  the  vessels  and  especially 
the  walls  of  the  small  veins  often  show  not  only  an  infiltration  of 
the  tissue  about  them,  but  a  growth  of  the  intima  which  leads  to  a 

271 


272  PATHOLOGY 

diminution  of  the  lumen.  In  the  cellular  infiltration  epithelioid 
and  giant  cells  may  be  found.  After  healing  an  indurated  cicatrix 
remains.  During  the  development  of  the  lesion,  extension  of  the 
infection  by  the  lymphatics  occurs,  which  is  shown  by  a  slowly 
developing  enlargement  and  induration  of  the  regional  lymph 
nodes.  At  the  same  time  the  virus  passes  into  the  blood  and  further 
foci  of  infection  develop,  characteristic  of  the  secondary  period. 
All  the  lymph  nodes  of  the  body  are  swollen,  indurated  and  painless. 
There  is  a  skin  eruption  which  takes  various  forms,  most  frequently 
appearing  as  a  roseola.  In  this  same  period  lesions  develop  on  the 
mucous  membrane  consisting  of  areas  of  hypertrophy  of  the 
papillae,  broad  condylomata.  The  swelling  is  due  to  infiltration, 
chiefly  of  lymphocytes  and  plasma  cells,  around  the  dilated  lymph 
and  blood  vessels  of  the  upper  layers  of  the  mucosa,  together  with 
proliferation  of  the  endothelium.  There  may  be  jaundice  at  this 
period,  which  can  be  referred  to  similar  processes  about  the  bile 
ducts,  and  anaemia  due  to  the  destruction  of  the  red  blood  corpuscles. 
The  lesions  in  the  tertiary  stage  consist  of  two  sorts,  one  of  diffuse 
chronic  interstitial  inflammations,  which  in  their  histological  ap- 
pearance present  nothing  characteristic  of  syphilis,  and  are  appar- 
ently due  to  the  effect  of  the  toxin  in  the  blood;  in  the  other  form 
there  are  produced  circumscribed  nodules  which  are  known  as 
gummata.  In  these  there  is  formation  of  granulation  tissue  which 
has  a  special  tendency  to  fatty  degeneration  and  to  caseation. 
When  of  recent  formation  the  gummata  appear  as  gelatinous  or 
firm  masses  of  granulation  tissue  with  yellow  foci.  In  a  later 
period  they  often  show  circumscribed  and  firm  islands  of  caseation 
in  a  white  cicatricial  tissue.  The  gummata  may  form  large  tumor- 
like  masses,  or  they  may  appear  as  microscopic  structures,  as  masses 
chiefly  of  lymphoid  cells,  disposed  to  necrosis.  The  granulation 
tissue  of  the  gummata  is  especially  rich  in  lymphocytes,  fibro- 
blasts  and  giant  cells  frequently  are  present.  With  the  removal 
of  the  cells  and  the  cessation  of  the  process,  the  gummata  heal, 
leaving  deep  cicatrices  which  may  become  adherent  to  neighboring 
organs.  Ulceration  and  destruction  of  tissue  can  be  very  extensive, 
and  may  affect  the  bones,  and  in  the  nose  may  destroy  the  support 
of  the  nasal  bones  producing  the  so-called  saddle  nose.  The 
caseation  develops  more  slowly,  the  foci  are  more  circumscribed 
and  firmer  than  is  the  caseous  tissue  of  the  tubercle.  Around  the 


TREPONEMA  PALLIDUM  273 

periphery  the  connective  tissue  extends  in  radiating  lines  into  the 
surrounding  tissue.  Such  gummata  frequently  are  seen  in  internal 
organs,  particularly  the  liver.  In  those  developing  in  the  sub- 
cutaneous tissue  and  in  the  periosteum  the  cellular  infiltration  is 
more  extensive,  there  is  a  greater  tendency  to  fatty  degeneration 
of  the  cells,  and  large  endothelial  cells  filled  with  fat  accumulate 
around  them.  The  process  often  is  complicated  by  suppuration 
due  to  pyogenic  infections.  Cicatrices  resulting  from  ulceration 
can  lead  to  extensive  stenosis  as  in  the  larynx,  in  the  trachea,  or  in 
the  intestines.  There  are  a  great  number  of  pathological  condi- 
tions of  the  central  nervous  system  produced  by  syphilis,  in  part 
focal  and  due  either  to  direct  action  of  the  organisms  or  to  results 
of  arterial  disease,  in  part  consisting  in  degenerations  of  nerve 
tracts  due  to  toxic  action.  Amyloid  disease  frequently  is  caused 
by  syphilis.  Although  the  association  of  many  of  these  lesions 
with  syphilis  has  been  definitely  established,  still  the  anatomical 
diagnosis  of  syphilis  in  this  late  stage  cannot  be  made  with  cer- 
tainty without  the  demonstration  of  the  treponema  in  the  lesions. 
Probably  the  most  characteristic  lesion  in  syphilis  is  the  implication 
of  the  vessels  in  the  pathological  process,  a  condition  found  in  all 
the  stages  of  the  disease.  In  the  early  lesions  there  are  acute  proc- 
esses around  and  within  the  vessels  in  the  foci,  and  in  the  late 
stages  lesions,  not  only  in  the  vessels  in  the  foci,  but  also  occurring 
independently.  The  small  arteries  of  the  base  of  the  brain  are  a 
place  of  predilection  for  syphilitic  changes.  The  difference  between 
the  syphilitic  changes  and  the  ordinary  arterio-sclerotic  changes  in 
these  vessels  lies  in  the  absence  of  calcification  and  macroscopical 
necrosis.  Microscopically,  there  is  cellular  infiltration  in  the 
adventitia  which  extends  into  the  surrounding  tissue  of  the  men- 
inges,  and  growth  of  the  intima  producing  narrowing  or  occlusion 
of  the  lumen.  The  internal  growth  may  be  concentric  or  more 
marked  on  one  side,  and  the  degenerative  changes  in  the  media, 
which  are  so  marked  in  nonsyphilitic  arterio-sclerosis,  are  absent. 
The  process  may  be  associated  with  thrombosis.  The  changes  in 
the  larger  arteries  which  frequently  lead  to  aneurysm  have  been 
considered. 

Congenital  infection  of  the  embryo  or  foetus  is  frequent,  and, 
in  certain  stages  of  disease  in  the  mother,  constant.  The  foetus 
frequently  dies  before  delivery  and  the  surface  epidermis  becomes 


274  PATHOLOGY 

macerated.  In  this  syphilis  of  the  newborn  the  lesions  have  the 
general  character  of  late  syphilis  and  a  few  or  many  organs  may 
be  affected.  There  is  no  primary  lesion.  Interstitial  changes  are 
more  prevalent  than  gummata.  The  gummata  may  appear  as 
miliary  or  larger  nodules.  The  most  frequent  condition  is  swelling 
of  the  spleen  and  the  condition  known  as  osteo-chondritis  syphilit- 
ica,  which  appears  at  the  diaphyso-epiphyseal  junction  as  a  yellow 
uneven  line,  at  which  point  separation  of  the  epiphysis  easily  takes 
place.  The  skin  shows  papullar  and  pustular  lesions.  There  are 
often  bullae  on  the  palms  of  the  hands  and  the  soles  of  the  feet.  In 
the  lungs  there  is  often  a  syphilitic  process  which  takes  the  form 
of  gummata  and  also  so-called  "white  pneumonia."  The  gummata 
are  yellowish  or  grayish  white,  are  not  sharply  circumscribed,  and 
usually  are  situated  beneath  the  pleura.  In  the  areas  of  white 
pneumonia  the  lung  is  firm  and  white  or  pale  red  in  color.  The 
alveolar  walls  are  greatly  thickened  and  the  contracted  air  spaces 
filled  with  desquamated  epithelium  and  leucocytes.  In  congenital 
syphilis  there  usually  are  lesions  in  the  adrenal  glands  and  pancreas 
consisting  in  fresh  inflammatory  cell  foci  with  necrosis.  Both 
gummata  and  interstitial  lesions  are  found  in  the  liver.  In  syphilis 
of  the  placenta  the  villi  are  thickened,  infiltrated  with  cells  and 
often  necrotic.  Ascites  and  general  dropsy  are  not  infrequent. 
The  organisms  are  especially  abundant  in  congenital  syphilis,  being 
found  in  all  organs  and  tissues  and  often  in  enormous  numbers. 
They  have  a  special  tendency  to  lie  in  the  walls  of  vessels  and  in  the 
tissue  spaces  about  them.  In  the  connective  tissue  spaces  their 
long  axis  is  in  the  direction  of  the  fibres.  In  the  skin  lesions  they 
often  are  found  in  great  numbers  between  the  epithelial  cells. 
They  rarely  are  found  within  the  cells.  They  may  be  found  in 
great  numbers  in  organs  in  which  the  syphilitic  changes  are  marked, 
and  in  other  cases  they  are  found  in  the  largest  numbers  in  organs 
which  show  little  or  no  alteration  and  are  few  or  absent  hi  organs 
most  affected,  seemingly  disappearing  with  the  advent  of  the  tissue 
reaction.  In  cases  of  tertiary  syphilis  the  parasites  are  infrequent, 
but  they  have  been  found  in  syphilitic  arteritis,  in  syphilitic  endo- 
carditis, in  the  tertiary  syphilis  of  the  skin,  and  in  fresh  gummata. 
SYPHILITIC  LESIONS  IN  GENERAL  are  characterized  by  their  pain- 
lessness.  This  is  due  in  part  to  their  slow  development  and  in  part 
to  the  fact  that  the  nerves  in  the  part  become  degenerated.  Exuda- 


TREPONEMA  PALLIDUM  275 

tion  as  a  rule  plays  but  little  part  in  the  formation  of  the  lesions. 
The  organisms  do  not  attract  polynuclear  leucocytes.  They  have, 
however,  been  occasionally  found  within  them.  Leucocytes  take 
part  in  the  production  of  the  lesions  only  when  there  is  associated 
necrosis.  The  syphilitic  organism  does  not  tend  to  the  production 
of  severe  destructive  lesions  in  the  tissue.  It  has  the  power  of 
active  proliferation,  but  the  tissues  have  a  high  degree  of  immunity 
toward  it.  With  a  little  less  virulence  on  the  part  of  the  organism, 
a  condition  closely  akin  to  a  symbiosis  might  be  established.  The 
organism  appears  to  have  a  similar  high  resistance  towards  the 
many  defensive  factors  in  the  body. 

IMMUNOLOGICAL  STUDY.  The  difficulty  of  experimentation  in 
the  disease  has  rendered  immunological  investigations  difficult. 
In  spite  of  this  fact,  however,  two  approximately  specific  reactions 
have  been  developed.  The  first,  the  so-called  Wassermann  re- 
action, is  almost  absolutely  specific  and  depends  upon  the  fact 
that  there  is  developed  in  the  blood  of  the  patient  a  substance 
which,  in  the  presence  of  a  lipoid  substance  obtained  principally 
from  the  livers  of  congenitally  syphilitic  infants  (also  from  guinea 
pig  hearts  and  from  various  other  normal  organs),  serves  to  fix  or 
bind  complement  so  that  it  cannot  complete  a  haemolytic  system. 
The  second,  the  so-called  luetin  reaction,  depends  upon  the  fact  that 
an  intracutaneous  injection  of  an  extract  of  pure  culture  of  tre- 
ponema  pallidum  produces,  in  the  syphilitic  patient,  a  wheal  or 
circumscribed  inflammatory  area.  The  luetin  reaction,  as  yet,  is 
not  so  firmly  established  as  a  diagnostic  measure  as  is  the  Wasser- 
mann reaction. 

A  CASE  OF  ACUTE  AND  CHRONIC  MITRAL  ENDOCARDITIS  ASSOCIATED 
WITH  NUMEROUS  OTHER  LESIONS  AND  INFECTIONS. 

Anatomical  Diagnoses.  Syphilis;  Acute  and  chronic  mitral  endo- 
carditis with  stenosis;  Hypertrophy  of  heart;  Arterio-sclerosis 
of  aorta;  Miliary  aneurysms  and  thrombosis  of  cerebral  arteries; 
Amyloid  degeneration;  Cirrhosis  of  liver;  Strictures  of  urethra; 
Operation  wound  in  perineum  with  opening  into  urethra;  False 
passage  in  urethra;  Chronic  urethritis;  Hypertrophy  of  bladder 
with  cystitis;  Purulent  infiltration  of  prostate;  Chronic  inflam- 
mation of  seminal  vesicles  with  atrophy;  Acute  pyelonephritis; 
Chronic  interstitial  orchids;  Operation  wound  in  mastoid;  Acute 


276  PATHOLOGY 

mastoiditis  and  otitis  media;  Acute  broncho-pneumonia;  Chronic 
fibrous  pleuritis;  Chronic  fibrous  peritonitis;  Streptococcus  and 
colon  bacillus  infection;  Streptococcus  septicaemia. 

Male,  negro,  age  thirty-five  years.  One  operation  had  been  performed 
in  order  to  open  and  drain  the  infected  mastoid  cells  and  another  to 
provide  an  opening  in  the  urethra  which  had  become  closed  by  stricture. 

Autopsy  seven  hours  post  mortem.  Body  well  developed,  well  nour- 
ished and  muscular.  Rigor  mortis  complete.  No  oedema.  In  the 
perineum  is  an  open  operation  wound  3  cm.  in  length.  Over  the  mastoid 
region  on  the  left  side  is  an  operation  wound  lined  with  dark  red  granula- 
tion tissue  which  extends  into  the  mastoid  cavities.  Subcutaneous  fat 
well  developed,  muscles  firm,  dark  red  in  color.  Below  the  meatus  the 
prepuce  is  adherent  to  the  glans  penis. 

Peritoneum.  The  omen  turn  is  adherent  to  the  abdominal  wall  at  two 
points,  to  the  right  and  left  of  the  bladder.  The  spleen  is  adherent  to 
diaphragm  by  masses  of  loose  fibrous  tissue,  as  is  also  the  right  lobe  of 
the  liver.  There  are  many  depressed,  irregularly  stellate,  opaque,  white 
thickenings  of  the  capsule  of  the  liver.  The  mesenteric  lymph  nodes  are 
prominent  and  on  section  firm  with  pale  centres. 

Pleurae.  Left  lung  at  the  apex  and  over  the  entire  base  is  adherent 
by  firm  fibrous  adhesions.  The  right  is  similarly  adherent  at  the  apex, 
posterior  border  and  edges  of  base. 

Pericardial  cavity  contains  a  small  amount  of  clear  fluid;  no  adhesions. 

Heart  weight  510  grams.  It  is  large  and  distended  with  liquid  blood 
which  clots  on  removal.  The  myocardium  is  firm,  the  wall  of  the  right 
ventricle  hypertrophied.  Valves  of  right  side  of  heart  are  normal.  The 
mitral  valve  segments  are  thickened  and  adherent  by  cartilage-like  tissue 
at  their  junction  on  the  right  side.  The  anterior  segment  of  the  valve 
is  calcified  near  its  attachment  and  the  auricular  surface  is  partly  covered 
with  translucent,  opaque  yellow  vegetations  some  of  which  are  easily 
detached.  The  free  edge  of  the  posterior  segment  is  thickened  and  the 
auricular  surface  contains  a  few  nodular  vegetations.  The  chordae 
tendineae  are  thickened  and  contracted.  The  wall  of  the  left  auricle  is 
slightly  thickened,  the  endocardium  rather  opaque.  The  coronary 
arteries  are  normal. 

Arteries.  In  the  ascending  portion  and  arch  of  the  aorta  there  are 
several  large  areas  of  sclerosis  almost  encircling  the  artery.  These  areas 
are  elevated  from  1-2  mm.,  the  surface  irregular;  in  some  the  centre  is 
lower  than  the  elevated  edges.  On  section  the  entire  thickness  of  the 
wall  shows  a  gray  opaque  tissue  with  no  clear  separation  of  intima  from 
media.  The  entire  artery  at  this  point  is  somewhat  dilated,  measuring 


TREPONEMA  PALLIDUM  277 

9  cm.  There  is  a  similar  large  white  elevated  area  midway  between  the 
cceliac  axis  and  the  bifurcation.  There  is  no  calcification.  The  other 
arteries  in  the  body  appear  normal. 

Lungs.  The  anterior  borders  of  both  lungs  are  emphysematous.  In 
the  upper  and  middle  lobe  of  the  right  lung  there  are  a  few  red  granular 
areas  of  solidification  around  the  bronchi,  a  very  few  similar  areas  in 
the  left  lung.  A  muco-purulent  fluid  can  be  expressed  from  the  bronchi. 
The  posterior  portions  of  both  lungs  are  congested  and  cedematous. 

Spleen  is  large,  weight  200  grams.  It  is  firm,  dark  red  in  color.  On 
section  the  surface  is  dark  red  with  small  rather  pale  homogeneous 
refractive  areas.  The  malpighian  bodies  not  prominent ;  trabeculae 
visible. 

Liver,  weight  1700  grams.  All  surfaces  show  irregular  linear  and 
stellate  thickenings  of  the  capsule  with  grayish  cicatricial  tissue  extend- 
ing from  these  into  the  liver.  On  section  red  with  pale  areas,  but  no 
distinct  nutmeg  appearance.  The  consistency  is  somewhat  increased. 
The  gall  bladder  and  ducts  are  normal. 

Gastro-intestinal  tract.    Mucosa  somewhat  injected,  otherwise  normal. 

Pancreas  normal. 

Kidneys  large,  weight  550  grams.  On  section  cortex  enlarged  and 
contains  pale  opaque  yellow  areas  and  lines  extending  from  pyramids. 

Adrenal  glands  normal. 

Testicles.  The  cavity  of  the  tunica  vaginalis  is  obliterated  on  both 
sides.  The  vasa  deferentia  are  converted  into  solid  white  fibrous  struc- 
tures. The  left  testicle  is  small  and  contains  a  yellowish  translucent 
mass  0.5  by  i  cm.  in  diameter.  The  remainder  of  the  testicle  is  hard  and 
the  tubules  do  not  thread.  The  right  testicle  is  small,  firm,  white,  the 
parenchyma  seemingly  reduced. 

Bladder.  The  walls  thickened.  The  mucosa  contains  dark  blue  black 
areas  of  hemorrhagic  extravasation  from  one  to  several  millimeters  in 
diameter.  Prostate  enlarged  and  indurated.  Pus  exudes  from  lower 
portion  on  section. 

Vesiculae  seminales  have  small  irregular  cavities  with  thickened  pig- 
mented  walls.  They  are  surrounded  by  dense  yellowish  fibrous  tissue, 
and  form  large  divergent  masses  behind  the  bladder. 

Urethra.  Posterior  to  entrance  of  the  operation  wound  which  is 
3  cm.  from  the  bladder  the  lumen  is  obliterated  and  there  is  a  false  pas- 
sage leading  into  the  bladder.  The  surrounding  tissue  is  fibrous  and 
contracted.  Throughout  its  course  the  mucosa  of  the  urethra  and  the 
tissue  about  it  is  thickened;  2  cm.  from  the  meatus  there  is  a  definite 
constriction  of  the  urethra  for  a  distance  of  2  cm. 

Bone  marrow.    That  of  femur  shows  some  increase  of  red  marrow. 


278  [PATHOLOGY 

Head.  Skull  thick,  sinuses  and  dura  normal.  There  is  some  clouding 
in  the  pia  arachnoid  but  no  exudate.  Vessels  at  base  of  brain  normal. 
No  macroscopic  lesion  of  brain  save  numerous  small  transparent  granula- 
tions on  surface  of  ventricles  and  a  number  of  small  red  points  (ap- 
parently dilated  vessels)  in  the  underlying  brain  tissue. 

The  left  middle  ear  is  filled  with  pus,  smears  from  which  show  large 
numbers  of  streptococci. 

The  spleen  and  kidneys  on  addition  of  iodine  give  the  amyloid  reaction. 
Both  cultures  and  smears  from  the  foci  of  suppuration  in  the  kidneys 
give  colon  bacilli.     Cultures  from  heart  blood  gave  abundant  colonies  of 
streptococci. 

Microscopic  examination  of  the  foci  of  broncho-pneumonia  show  the 
bronchi  filled  with  pus  and  in  the  surrounding  alveoli  fibrino-purulent 
exudation.  There  is  considerable  oedema  of  the  peribronchial  tissue  and 
infiltration  with  polynuclear  leucocytes,  lymphoid  and  endothelial  cells. 
In  the  purulent  exudate  in  the  bronchi  there  are  short  chains  of  strep- 
tococci and  within  the  cells  numerous  diplococci.  The  testicles  show 
well  marked  increase  in  the  interstitial  tissue  with  atrophy  of  tubules. 
The  nodular  area  in  the  left  testicle  is  composed  of  dense  connective 
tissue  with  no  traces  of  tubules  within  it. 

The  kidneys  show  foci  of  purulent  infiltration  extending  throughout 
cortex.  Pus  cells  in  large  numbers  are  contained  in  the  tubules.  The 
glomeruli  are  enlarged  and  show  hyalin  masses  (amyloid)  along  the 
capillaries. 

The  follicles  of  the  spleen  are  slightly  enlarged  and  contain  foci  of 
amyloid. 

In  the  liver  the  connective  tissue  along  many  of  the  portal  spaces  is 
increased  in  amount  and  infiltrated  with  cells.  The  condition  varies 
greatly  in  different  parts.  The  central  veins  and  capillaries  are  dilated 
and  the  liver  cells  between  them  atrophied. 

A  section  of  the  lateral  ventricle  of  the  brain  shows  the  small  granules 
on  the  surface  to  be  composed  of  neuroglia  tissue.  The  section  passed 
through  several  of  the  red  points  noticed  and  shows  these  to  be  due  to 
aneurysm  formation.  The  wall  of  the  dilated  vessel  is  hyalin,  and 
presses  upon  the  surrounding  brain  tissue,  the  perivascular  space  being 
obliterated.  In  several  of  the  arteries  in  the  section  there  is  a  similar 
degeneration  of  the  wall  and  a  formation  of  small  mural  thrombi. 

REMARKS.  The  case  offers  a  singular  variety  of  lesions,  most 
of  them  due  to  past  and  present  infectious  processes.  The  chronic 
fibrous  peritonitis  and  pleuritis  call  for  no  special  consideration. 
The  lesions  in  the  gemto-urinary  system  can  be  taken  together. 


TREPONEMA  PALLIDUM  279 

There  has  been  a  primary  and  long  enduring  gonorrheal  infection 
which  has  produced  the  chronic  urethritis  and  strictures,  and  by 
extension  to  the  epididymes,  testicles  and  seminal  vesicles,  atrophy, 
destruction   and   chronic  induration   of   these  structures.      (The 
possible  influence  of  syphilis  in  their  causation  cannot,  however,  be 
excluded.)     The  operation  in  the  perineum  was  performed  to  open 
the  constricted  urethra.     The  hypertrophy  of  the  bladder  was  the 
result  of  the  increased  muscular  effort  necessary  to  discharge  its 
contents  through  the  constricted  urethral  canal.     The  cystitis  may 
have  existed  prior  to  the  operation  or  may  have  been  produced  by 
a  subsequent  infection.     Infection  easily  occurs  in  such  cases. 
The  infection  extended  into  the  prostate  and  along  the  ureters  into 
the  kidneys.     This  condition  of  acute  suppurative  nephritis  in 
association  with  acute  cystitis  is  not  uncommon.     It  is  not  neces- 
sary to  assume  that  the  organisms  actually  travel  up  the  ureter, 
but  the  infection  extends  by  continuity  of  the  infected  fluid.    The 
chronic  and  acute  endocarditis  may  represent  a  separate  infection 
or  it  may  have  been  due  to  the  gonorrheal  infection.    This  has  led 
to  hypertrophy  of  the  right  side  of  the  heart  and  to  general  passive 
congestion  which  was  not  sufficiently  marked  to  have  produced 
oedema.    The  diagnosis  of  syphilis,  although  probable,  must  in  the 
absence  of  clinical  history,  Wassermann  test  and  the  formation  of 
definite  gummata,  remain  uncertain.    In  its  favor  are  the  amyloid 
degeneration,  the  character  of  the  arterio-sclerosis  in  the  aorta,  the 
coarse  bands  of  connective  tissue  in  the  liver  and  the  extensive 
interstitial  changes  and  atrophy  in  the  testicles.    The  last  would 
have  been  more  characteristic  of  syphilis  had  the  testicles  alone 
been  affected  without  involvement  of  the  rest  of  the  genito-urinary 
system.    The  miliary  aneurysms  of  the  brain  may  have  been  due 
to  degeneration  of  the  arterial  walls  caused  by  syphilis,  although 
no  morphological  or  statistical  evidence  of  the  association  has  been 
adduced.    The  acute  otitis  media  and  the  mastoiditis  for  which  an 
operation  had  been  performed  were  probably  due  to  infection  of 
the  middle  ear  extending  from  the  throat.     Streptococci  were  found 
in  the  pus  from  the  middle  ear.    The  foci  of  broncho-pneumonia 
are  due  to  infection  with  streptococci  and  pneumococci,  these 
entering  into  the  lung  by  the  bronchi.    A  terminal  streptococcus 
septicaemia  is  not  uncommon.     The  organisms  may  have  been 
carried  into  the  blood  from  several  foci. 


STREPTOTHRIX  ACTINOMYCES   (ACTINOMYCES  Bovis) 

This  is  an  organism  belonging  to  the  trichomycetes  or  filamentous 
branching  bacteria.  In  the  tissues  the  masses  of  organisms  appear 
as  pale  yellow  granules,  i  mm.  or  more  in  size.  Microscopic  ex- 
amination shows  the  periphery  of  the  granules  to  be  composed  of 
radiating  club  or  pear-shaped  bodies  closely  set  together,  to  which 
appearance  is  due  the  name  "ray  fungus."  In  association  with 
these  bodies  or  independently,  branching  filaments  are  found. 

Infection  in  man  occurs  in  the  alimentary  canal  leading  to  the 
formation  of  large  tumor-like  masses  of  granulation  tissue,  in  the 
interior  of  which  are  found  foci  of  suppuration  around  masses  of 
the  organisms.  The  infection  often  occurs  in  the  jaws  and  around 
the  teeth,  and  secondary  foci  may  form  in  the  internal  organs. 

A  CASE  or  ACTINOMYCOSIS 

(Only  that  part  of  the  autopsy  which  has  immediate  reference  to  the 

lesions  is  quoted.) 

Anatomical  Diagnoses.  Actinomycosis  (primary  in  right  inferior 
maxilla  with  extensions  in  the  subcutaneous  tissue  of  face  and 
neck,  into  the  temporal  bone  and  into  brain  producing  multiple 
abscesses) ;  Metastases  in  liver. 

White,  male,  age  fifty-two  years.  The  entire  right  side  of  face  and 
neck  is  greatly  swollen,  indurated  and  below  the  angle  of  the  jaw,  are 
three  discharging  sinuses  with  retracted,  indurated  margins.  In  the 
subcutaneous  tissue  on  this  side  of  the  neck  are  numerous  foci  of  pus 
varying  in  size  from  0.2-1  cm.  in  diameter  and  embedded  in  extremely 
dense,  pearly  gray  tissue.  The  pus  contains  yellow  firm  granules,  smears 
from  which  show  Gram  staining,  branching  filaments.  There  is  a  small 
blue  red  tumor  mass  i  cm.  in  diameter  projecting  from  the  inner  surface 
of  the  gum  at  the  base  of  the  left  inferior  canine  tooth.  Upon  removing 
the  tissue  from  the  right  temporal  region,  the  bone  is  bare,  soft  and 
necrotic.  + 

The  dura  is  closely  adherent  to  bone  beneath  the  temporal  fossa.  It 
is  attached  to  the  pia-arachnoid  over  the  inferior  portion  of  the  right 
temporal  lobe,  but  is  free  elsewhere.  The  cerebral  sulci  are  shallow,  the 

280 


STREPTOTHRDC  ACTINOMYCES  281 

cerebral  surface  unusually  smooth.  The  right  temporal  lobe  of  the  brain 
is  enlarged.  On  section  it  contains  a  large  pocket  of  green  semifluid 
pus,  and  in  the  vicinity  of  this  there  are  several  smaller  abscesses.  The 
wall  of  the  large  abscess  has  a  tough  lining  membrane  in  which  are  visible 
some  small  yellow  tubercles.  The  odor  of  the  abscess  contents  is  very 
offensive.  Both  lateral  ventricles  are  slightly  dilated.  Section  of  basal 
nuclei  shows  a  small  haemorrhage  on  the  right  side  external  to  and  just 
below  the  lenticular  nucleus.  This  haemorrhage  is  i  cm.  hi  diameter  and 
reaches  the  inner  margin  of  one  of  the  smaller  abscesses  in  the  right 
temporal  lobe.  In  the  right  middle  fossa  of  the  skull  are  two  small 
perforations  of  the  squamous  portion  of  the  temporal  bone  which  com- 
municates directly  with  a  small  subcutaneous  abscess  in  the  right  tem- 
poral fossa.  The  larger  abscess  in  the  temporal  lobe  is  immediately  over 
this  region.  The  adjoining  bone  is  roughened  and  necrotic. 

The  weight  of  the  liver  is  1500  grams.  On  the  diaphragmatic  surface 
of  the  right  lobe  there  is  a  slightly  elevated,  yellow-white  area  2  cm.  in 
diameter  extending  a  distance  of  2  cm.  into  the  hepatic  substance.  On 
section  this  nodule  is  firm,  gray,  with  minute  yellow  foci  i  mm.  in  diam- 
eter within  its  substance.  The  liver  otherwise  normal. 

On  microscopical  examination  of  the  tissues,  numerous  masses  of  the 
organism  were  found  everywhere.  They  lay  within  pus  pockets  in  the 
midst  of  a  dense  cicatricial  connective  tissue. 

REMARKS.  The  case  illustrates  the  great  tendency  of  the  in- 
fection to  extend  locally  along  the  surface  of  bone.  The  infection 
probably  began  in  a  tooth  in  the  alveolar  process  of  the  lower  jaw 
and  from  this  extended  over  the  body  and  the  ascending  ramus  to 
the  base  of  the  skull  producing  necrosis  and  perforation  followed 
by  hemorrhage  and  abscess  in  the  brain.  The  metastases  in  the 
liver  is  by  means  of  the  blood  vessels. 


BACILLUS   MALLEI 

The  glanders  bacillus  is  a  small  rod  with  rounded  ends  and  is 
somewhat  variable  in  length.  It  produces  no  spores,  has  no 
flagella,  and  is  decolorized  by  the  Gram  stain.  The  organism  is 
pathogenic  for  guinea  pigs  and  rabbits.  Inoculation  of  guinea  pigs, 
either  subcutaneously  or  in  the  peritoneal  cavity,  produces  a 
characteristic  acute  swelling  and  inflammation  of  the  testicle. 
In  man  the  disease  is  not  infrequent,  the  infection  almost  invariably 
being  acquired  from  the  horse.  It  appears  in  the  acute  and  chronic 
form,  the  lesions  in  man  having  much  similarity  to  -the  same  forms 
of  disease  hi  horses.  In  the  chronic  form  the  infection  may  persist 
for  years,  producing  repeated  abscesses,  usually  in  the  muscles. 
The  lesions  consist  in  inflammation  with  purulent  exudation  and 
softening,  there  being  a  marked  tendency  to  destruction  of  nuclei 
and  formation  of  nuclear  detritus.  Large  endothelial  giant  cells 
not  uncommonly  are  present.  The  bacilli  exert  their  action  by  an 
endotoxin  which  may  be  obtained  from  the  dead  bacilli. 

A  CASE  OF  ACUTE  GLANDERS  m  MAN* 

Anatomical  Diagnoses.  Glanders;  Haemorrhage,  ulceration  and 
pustule  formation  in  skin;  Abscesses  in  muscles  and  in  lungs; 
Acute  pleurisy;  Acute  parenchymatous  degeneration. 

White  male,  age  thirty  years.  Clinical  history.  On  September  3Oth, 
while  skinning  a  horse  which  had  died  of  glanders,  he  cut  his  finger.  The 
next  day  the  finger  pained  him  but  did  not  appear  to  be  injured.  Eight 
days  later  he  was  seen  by  a  physician  who  incised  the  finger.  He  re- 
mained in  bed  complaining  of  fever  with  great  thirst  until  October  24th, 
when  he  was  admitted  into  the  hospital  and  the  finger  was  amputated. 
On  the  fourth  day  after  admission,  pustules  appeared  on  the  forehead 
and  upon  other  parts  of  the  body.  Later  those  on  the  forehead  became 
confluent  and  ulcerated.  Death  occurred  November  ist. 

Autopsy  five  hours  after  death.  The  body  is  that  of  a  well-built, 
muscular  man.  Subcutaneous  fat  moderate  in  amount.  Rigor  mortis 
very  marked.  Slight  lividity  of  dependent  portions.  Amputation  of 
finger. 

*  J.  H.  Wright,  Journal  of  Experimental  Medicine. 
282 


BACILLUS  MALLEI  283 

The  skin  of  the  forehead  as  low  as  the  eyebrows  and  of  the  scalp  as  far 
back  as  the  vertex  is  thickened,  discolored,  eroded,  and  feels  dense  to 
the  touch.  The  margin  of  this  area  is  escalloped,  and  is  rather  sharply 
elevated  above  the  adjoining  normal  skin.  In  color  it  is  purple,  mottled 
with  small  yellow  areas.  Over  the  upper  portion  of  the  forehead  and 
at  the  beginning  of  the  scalp,  the  epidermis  is  purple  to  black  in  color, 
and  more  or  less  detached  from  the  underlying  tissue,  from  which  it  can 
easily  be  removed.  In  places  it  is  lacking,  leaving  irregular  and  rather 
superficial  ulcerations,  in  which  there  can  be  made  out  many  yellow 
specks,  not  soft  enough  to  be  called  pus.  On  section  the  tissue  is  deeply 
infiltrated  with  an  opaque,  yellowish-white  material,  which  is  rather 
firm,  and  can  not  be  squeezed  out  like  pus.  In  the  left  upper  eyelid  are 
several  pustules,  single  and  grouped.  Over  the  zygomatic  arch  and  on 
the  right  side  there  are  also  two  small  groups  of  pustules.  In  the  skin 
of  the  left  arm,  on  its  outer  and  posterior  surfaces,  are  scattered  several 
pustules  from  1-3  mm.  in  diameter  and  about  i  mm.  in  elevation.  Three 
or  four  similar  pustules  are  seen  on  the  skin  of  the  right  arm,  and  one  on 
the  skin  over  the  tibia.  On  the  front  of  the  chest  are  two  pustules, 
besides  a  small  group  below  the  outer  end  of  the  left  clavicle.  The  pus- 
tules found  in  these  situations  generally  present  a  purplish  tint  about 
their  bases.  In  the  pectoral  muscles  on  the  right  side,  near  the  sterno- 
clavicular  articulation,  is  a  small,  oval,  yellow,  semi-solid  nodule  about 
the  size  of  a  split  pea.  The  left  axilla  contains  an  area  of  suppuration  in 
the  axillary  fatty  tissue  about  5  cm.  long  and  3  cm.  in  diameter.  On 
section,  this  area  resembles  a  bit  of  very  coarse  sponge,  the  meshes  of 
which  are  filled  with  a  thin,  odorless,  yellowish  fluid.  Some  of  the 
lymph  nodes  in  the  neighborhood  are  still  well  preserved,  although  con- 
siderably enlarged,  and  on  section  they  show  a  yellow  infiltration  on  the 
side  toward  the  pus. 

Lungs.  The  left  lung  over  the  upper  lobe  is  bound  down  by  fibrous 
adhesions.  The  right  lung  is  free.  Both  are  moderately  congested, 
and  slightly  cedematous  posteriorly.  On  the  lower  surface  of  the  right 
upper  lobe  are  two  yellow,  elevated  areas,  2  mm.  in  diameter,  surrounded 
by  a  dark  red  zone.  The  pleura  over  both  areas  is  covered  with  a  thin 
coat  of  fibrin.  Scattered  through  the  remainder  of  the  right  lung, 
usually  just  beneath  the  pleura,  are  in  all  about  a  dozen  small  resistant 
areas,  the  largest  not  more  than  i  cm.  in  diameter.  On  section,  some 
of  these  areas  are  found  to  be  solid,  of  a  dark  red  color,  with  yellow 
pouits;  others  softened  or  broken  down,  forming  abscesses  or  cavities 
filled  with  fluid  of  a  purulent  character.  On  the  pleura  over  these  areas 
there  is  in  many  places  a  thin  fibrinous  exudate. 

Heart.    Not  remarkable. 


284  PATHOLOGY 

Spleen.  Enlarged  to  half  again  its  normal  size;  soft.  Follicles  not 
visible  on  section. 

Kidneys.  Capsule  very  slightly  adherent.  On  section,  cortex  more 
opaque  than  normal.  Pyramids  injected. 

Liver.    Slight  cloudy  swelling. 

The  deep  cervical  and  mesenteric  lymph  nodes  slightly  enlarged  and 
congested. 

The  nasal  cavities  and  pharynx  not  examined. 

Bacteriological  Examination.  Cover-glass  preparations  from  the 
lesions  on  the  scalp  and  from  the  pus  of  the  axillary  abscess  show  the 
presence  of  a  few  bacilli  of  medium  size,  with  rounded  ends,  varying  in 
length,  and  having  faintly  staining  spaces  in  the  protoplasm.  The 
purulent-looking  fluid  from  a  small  abscess  cavity  in  the  lung  is  negative 
on  cover-glass  examination.  Cultures  were  made  on  coagulated  blood 
serum  (Loffler's  mixture)  in  test  tubes  from  the  various  lesions  and  from 
the  organs  and  show  glanders  bacilli.  Inoculation  of  guinea  pigs  with 
pure  cultures  give  the  usual  lesions  in  the  testicle. 

REMARKS.  The  case  is  a  simple  one.  A  primary  infection  of 
the  finger  with  metastases  in  the  skin  and  muscles.  The  pustules 
in  the  skin  which  are  produced  in  these  acute  cases  may  present 
some  similarity  to  the  pustules  of  smallpox  and  the  diseases  have 
been  confounded.  The  resemblance  is  but  superficial  clinically 
and  there  is  no  histological  similarity  between  the  lesions  of  the 
two  diseases.  In  the  cutaneous  pustules  of  glanders  the  epithelial 
lesions  characteristic  of  smallpox  are  absent,  the  infiltration  of  the 
corium  is  more  extensive  and  the  lymphatic  vessels  are  extensively 
involved  in  the  process. 


BACILLUS  ANTHRACIS 

This  is  an  organism  of  great  medical  interest  because  the  first 
proof  of  the  production  of  disease  by  bacteria  was  given  in  anthrax. 
The  organism  is  a  large  bacillus  staining  easily  with  the  ordinary 
bacterial  stains  and  with  Gram.  It  grows  easily  on  the  ordinary 
culture  media  at  wide  temperature  limits,  having  saprophytic  as 
well  as  parasitic  growth.  On  artificial  media  the  bacilli  form  long 
tangled  threads.  In  the  presence  of  oxygen  it  forms  spores  which 
are  very  resistant.  It  is  highly  infectious  for  white  mice,  rabbits 
and  guinea  pigs  and  produces  one  of  the  natural  diseases  of  cattle. 
The  synonym  "milzbrand"  or  "splenic  fever"  has  its  origin  in  the 
constantly  present  acute  swelling  of  the  spleen. 

The  infection  may  be  transmitted  from  animals  to  man,  either 
from  the  carcasses  or  by  handling  hides  or  wool  which  contain  the 
spores  of  the  bacilli.  Three  types  of  the  disease  may  be  distin- 
guished in  man  depending  upon  the  locality  of  the  infection.  An- 
thrax of  the  skin  appears  in  the  form  of  the  anthrax  carbuncle  and 
as  an  inflammatory  oedema.  The  microscopic  appearances  in  the 
carbuncle  are  characteristic.  The  bacilli  appear  in  the  greatest 
number  hi  the  upper  layer  of  the  corium  and  in  the  papillary  bodies. 
There  is  an  extensive  and  deep  infiltration  with  fibrin,  pus  cells 
and  red  corpuscles,  accompanied  with  necrosis.  The  organisms 
extend  by  the  lymphatics  to  the  adjacent  lymph  nodes  and  later 
into  the  blood,  but  the  infection  of  the  blood  is  not  so  common  in 
man  as  hi  animals.  Infection  of  the  intestine  produces  large 
necrotic  haemorrhagic  foci  with  great  oedema  of  the  surrounding 
tissue.  Infection  of  the  lung  results  from  the  inhalation  of  the 
spores  (wool  sorter's  disease)  and  takes  the  form  of  large  haemor- 
rhagic purulent  foci. 


285 


286  PATHOLOGY 


A  CASE  OF  ANTHRAX  IN  MAN 

Anatomical  Diagnoses.  Surgical  wound  of  neck  (removal  of  area 
of  primary  infection  with  bacillus  anthracis) ;  Bacillus  anthracis 
septicaemia;  Acute  haemorrhagic  cerebrospinal  meningitis;  Acute 
focal  haemorrhagic  enteritis;  Acute  mesenteric  lymph  noditis; 
Acute  splenitis;  Acute  degeneration  of  heart,  liver  and  kidneys; 
Bilateral  hydrocele. 

Patient  white,  age  forty-seven  years,  a  teamster  employed  in  handling 
hides,  entered  hospital  complaining  of  a  painful  swelling  on  the  left  side 
of  neck.  This  appeared  three  days  previously  as  a  small  red  point  and 
has  rapidly  increased  in  size.  On  the  left  side  of  the  neck,  in  the  middle, 
and  a  little  posterior  to  the  line  of  ear,  is  a  hard,  dark  crust.  The  centre 
of  the  swelling  is  elevated  i  cm.  above  the  neck  level  and  extends  over 
an  area  of  3  cm.  The  intense  induration  of  the  centre  gives  place  to  a 
slight  oedema  at  the  edges.  Complains  also  of  headache,  loss  of  appetite 
and  general  discomfort.  Temperature  103  degrees.  The  indurated 
area  in  the  neck  was  removed.  Patient  died  three  days  later  in  coma 
which  followed  delirium.  A  blood  culture  taken  before  death  showed  a 
pure  growth  of  the  bacillus  anthracis  averaging  180  colonies  to  i  c.c.  of 
blood. 

Body  is  that  of  an  exceptionally  well  developed,  muscular,  well  nour- 
ished man.  There  is  slight  rigor  mortis  and  post  mortem  congestion. 
There  is  no  oedema;  external  orifices  normal.  On  the  left  side  of  the 
neck  hi  the  middle  there  is  an  oval  surgical  wound  6  by  4  cm.  In  this 
area  the  skin  and  subcutaneous  tissue  has  been  removed,  leaving  a  clean 
wound  which  extends  downwards  to  the  deep  muscles  of  the  neck. 
Around  this  wound  there  is  slight  oedema.  Subcutaneous  fat  in  fair 
amount,  firm  and  yellow,  the  muscles  of  thorax  and  abdomen  firm  and 
dark  red. 

The  peritoneum  is  smooth,  pale  and  glistening,  except  for  areas  over 
two  of  the  mesenteric  lymph  nodes  and  over  a  small  swollen  area  on  the 
mesentery  and  intestine  32  cm.  from  the  ileo-caecal  valve.  The  peri- 
toneum over  the  lymph  nodes  is  slightly  injected,  and  over  the  swollen 
area  mentioned  the  intestine  is  deeply  injected  and  cloudy.  There  are 
no  peritoneal  adhesions.  The  mesenteric  lymph  nodes  are  slightly 
swollen  and  reddish  on  section.  There  are  two  glands  adjacent  to  the 
injected  area  of  the  intestine  which  are  considerably  swollen,  2  by  i  cm., 
and,  on  section,  deep  red,  their  centres  soft.  The  tissue  about  them  is 
injected. 

Pleurae.    The  lungs  free  from  adhesions.    Pleurae  smooth. 


BACILLUS  ANTHRACIS  287 

Heart.  Pericardium  contains  a  small  amount  of  clear  fluid.  Weight 
of  heart  412  grams.  On  section  the  myocardium  is  mottled  with  red 
and  pale  areas.  The  pale  areas  are  irregularly  distributed  from  2-8  mm. 
in  diameter,  generally  longitudinal  in  shape,  corresponding  to  the  direc- 
tion of  the  muscle  fibres.  They  are  circumscribed  and  in  them  the  myo- 
cardium is  softer.  The  cardiac  valves  and  coronary  arteries  are  normal. 
The  blood  within  the  heart  is  fluid  and  is  very  dark  in  color.  The  left 
ventricle  contracted  2  cm.  in  thickness,  the  right  6  mm. 

Lungs  are  crepitant  throughout.  Both  lower  lobes,  especially  pos- 
terior portions,  are  congested,  dark  red  in  color,  and  on  section  a  thin, 
blood-stained  fluid  escapes. 

Spleen.  Weight  350  grams.  Capsule  is  smooth  and  glistening.  On 
section  a  dark  chocolate-brown,  the  markings  and  malpighian  bodies 
indistinct.  Pulp  is  soft  and  projects  from  the  cut  surface. 

Gastro-intestinal  tract.  Stomach  normal.  In  the  ileum,  32  cm.  from 
the  caecum,  there  is  a  swollen  haemorrhagic  area  3  by  2  cm.  in  size  corre- 
sponding to  the  swelling  at  the  mesenteric  attachment.  Within  the 
intestine  at  this  point  there  is  a  dark  red  exudate.  The  remainder  of 
the  canal  is  normal. 

Pancreas  normal. 

Liver.  Weight  2040  grams.  The  capsule  smooth.  Pale  brown  in 
color.  On  section  slight  central  congestion  of  the  lobules. 

Kidneys.  Weight  462  grams.  The  cortex  is  i  cm.  in  thickness, 
rather  pale  and  opaque.  Capsule  strips  easily.  Markings  normal. 

Adrenals  normal. 

Genitalia.  The  tunicae  vaginales  on  both  sides  are  distended  with 
clear  fluid.  Testicles  and  epididymes  normal. 

Mouth,  throat,  and  organs  of  neck  normal. 

Brain,  meninges  and  cord.  Scalp  and  calvarium  normal.  On  re- 
moval of  dura  there  is  an  abundant  haemorrhagic  fibrinous  exudation,  in 
places  3  mm.  in  thickness,  in  the  meshes  of  the  pia  arachnoid,  which 
gives  the  appearance  of  a  blood  clot  and  extends  over  both  lateral  hemi- 
spheres and  cerebellum  and  to  a  less  extent  over  the  pons  and  medulla- 
There  is  no  exudation  on  the  surface  of  the  pia.  On  section  of  brain 
the  exudate  extends  into  the  sulci  and  within  the  brain  tissue  there  are 
numerous  small  punctate  dark  red  areas  most  of  which  remain  after 
wiping.  In  the  ventricles  a  small  amount  of  reddish  fluid.  The  upper 
half  of  the  spinal  cord  is  surrounded  by  a  subpial  haemorrhagic  exudate, 
which  is  smaller  in  amount  than  that  in  the  cerebral  meninges  and  gradu- 
ally fades  out  below.  The  vessels  of  cord  are  injected. 

Bacillus  anthracis  found  in  smears  of  blood  and  in  cultures  from  all 
organs. 


288  PATHOLOGY 

Microscopic  examination  of  the  primary  lesions  shows  infiltration  of 
the  entire  area  with  a  haemorrhagic  fibrino-purulent  exudate.  This  lies 
in  the  corium,  in  the  subcutaneous  tissue  and  around  the  muscle  fibres 
in  the  lower  part  of  the  section.  Immediately  beneath  the  epidermis 
the  exudate  is  less  marked  and  is  more  cedematous  in  character.  The 
fibres  of  the  corium  appear  as  widely  separated  bundles.  The  fat  tissue 
is  destroyed,  the  fat  cells  not  visible  as  such,  but  in  their  place  are  numer- 
ous round  or  oval  clear  spaces.  The  exudate  varies  somewhat  in  char- 
acter; there  are  places  where  the  tissue  is  filled  with  red  blood  corpuscles 
and  in  other  places  it  contains  chiefly  polynuclear  cells.  All  the  blood 
vessels  are  widely  dilated,  there  is  mural  arrangement  of  leucocytes  and 
in  the  walls  are  emigrating  leucocytes.  In  several  of  the  veins  and 
arteries  there  is  active  proliferation  of  the  endothelial  cells  forming  a 
thick  cellular  lining.  Large  bacilli  are  found  in  small  numbers  in  the 
exudate  and  are  more  numerous  just  beneath  the  epidermis.  Sections 
of  the  brain  and  meninges  show  a  dense  haemorrhagic  and  fibrinous 
exudate  infiltrating  the  arachnoid.  In  this  there  are  widely  dilated 
vessels.  The  exudate  extends  into  the  sulci  and  to  some  extent  is  seen 
in  the  peri  vascular  spaces  of  the  vessels  entering  the  brain.  Deeper  in 
the  brain  there  are  foci  of  haemorrhage  in  dilated  perivascular  spaces. 
The  brain  tissue  around  the  exudate  is  cedematous.  Bacilli  in  small 
numbers  are  found  in  the  exudate. 

Sections  of  the  haemorrhagic  area  in  the  intestine  show  an  intense 
haemorrhagic  fibrinous  exudate  throughout  the  entire  intestinal  wall  and 
extending  into  the  attached  mesentery.  There  is  considerable  necrosis 
of  the  mucous  membrane  with  desquamation  of  epithelium. 

The  enlarged  mesenteric  lymph  nodes  show  a  haemorrhagic  infiltration 
with  much  fibrin  in  the  dilated  sinuses,  with  considerable  necrosis  and 
haemorrhage  in  the  follicles. 

The  spleen  shows  intense  congestion  and  haemorrhage.  In  the  tissue 
there  are  large  numbers  of  bacilli. 

Heart,  liver  and  kidneys  show  marked  cloudy  swelling  and  fatty 
degeneration,  this  latter  being  particularly  marked  in  the  heart. 

REMARKS.  A  typical  case  of  anthrax.  The  primary  infection 
of  neck  probably  resulted  from  carrying  infected  hides  on  the  shoul- 
ders. There  are  secondary  foci  of  infection  in  the  meninges  and  in 
the  alimentary  canal  and  infection  of  the  blood  (septicaemia).  The 
acute  enlargement  of  the  spleen  is  due  to  congestion  and  haemor- 
rhage and  forms  one  of  the  most  characteristic  anatomical  lesions  of 
the  disease.  (Synonym:  splenic  fever.)  The  weight  of  the  heart 


BACILLUS  ANTHRACIS  289 

is  unusual,  but  in  consideration  of  the  occupation,  which  demands 
heavy  labor,  the  size,  muscular  development  and  good  nutrition  of 
the  individual,  the  rapid  death  and  the  acute  degeneration  should 
not  be  regarded  as  pathological.  The  same  may  be  said  of  the 
increased  weight  of  liver  and  kidneys. 

The  anthrax  bacillus  in  the  tissues  produces  necrosis  with  haemor- 
rhagic  fibrinous  exudation.  In  these  lesions  the  necrosis  of  tissue 
is  obscured  by  the  exudate  and  in  the  primary  lesion  is  shown  only 
by  the  spaces  occupied  by  the  fat  globules  which  have  been  freed 
by  the  destruction  of  the  cells. 


BACILLUS   DIPHTHERLE 

Diphtheria  is  a  typical  toxic  disease.  The  diphtheria  bacilli  are 
slender,  straight  or  slightly  curved  rods,  rarely  of  uniform  thickness 
throughout.  They  may  be  club-shaped  at  one  or  both  ends  and 
occasionally  are  thickened  at  the  centre.  The  organisms  are  easily 
stained  and  in  certain  cases  appear  to  be  traversed  by  transverse 
bands  which  give  them  a  striped  appearance.  They  produce  no 
spores  and  are  nonmotile.  Growth  takes  place  readily  on  most 
of  the  laboratory  media,  the  most  widely  used  medium  being  coagu- 
lated blood  serum.  The  organism  grows  at  temperatures  varying 
between  19  and  42°  C.,  and  is  probably  an  exclusive  parasite.  It  is 
pathogenic  for  most  of  the  laboratory  animals.  Infection  in  man 
takes  place  in  the  mucous  membrane  of  the  tonsils,  uvula,  pharynx; 
more  rarely  in  the  nasal  passages  and  the  larynx.  The  surfaces 
affected  are  covered  with  a  gray,  yellow-gray  or  brown  membrane 
which  adheres  more  or  less  firmly  and  when  removed  leaves  a 
surface  deprived  of  epithelium.  When  the  membrane  formation 
extends  into  the  trachea  it  is  easily  removed  and  often  separates 
subcutaneously  in  the  form  of  a  large  cast.  The  membrane  varies 
hi  structure  in  different  places.  It  is  composed  chiefly  of  fibrin  in 
the  form  of  a  meshwork  with  openings  of  various  sizes,  the  long 
diameters  of  which  are  parallel  to  the  surface.  A  variable  number 
of  degenerated  leucocytes  are  enclosed  in  the  fibrin.  When  the 
membrane  forms  over  a  thick  squamous  epithelium  the  epithelial 
cells  take  part  in  its  structure.  The  cells  undergo  a  hyalin  change; 
the  edges  of  the  cells  unite  and  form  a  reticulum  in  which  the  spaces 
represent  the  places  formerly  occupied  by  the  nuclei.  The  fibrin 
on  the  surface  is  found  in  association  with  a  fibrinous  exudate  which 
extends  into  the  tissue.  This  often  is  combined  with  a  haemorrhagic 
exudation  and  extensive  necrosis.  The  local  lesions  leading  to 
membrane  formation  consist  hi  necrosis  of  the  surface  and  an 
inflammatory  exudation  in  the  tissue  beneath,  which,  in  contact 
with  the  necrotic  cells,  coagulates  and  produces  the  characteristic 
membrane.  The  bacilli  have  little  or  no  tendency  to  invade,  they 
grow  in  and  on  the  surface  of  the  membrane  and  produce  there  a 

290 


BACILLUS  DIPHTHERLE  291 

toxin  which  is  absorbed  and  leads  to  degenerative  changes  in  the 
internal  organs.  Toxic  substances  of  the  same  character,  as  those 
produced  by  the  bacilli  when  growing  on  the  surface,  are  produced 
in  culture  media,  and  lesions  similar  hi  character  to  those  of  the 
internal  organs  produced  by  the  disease  may  be  produced  in  animals 
by  injecting  them  with  fluid  cultures  from  which  the  bacilli  have 
been  removed  by  filtration.  The  bacilli  occasionally  invade  the 
tissues  and  produce  in  them  exudates  of  a  fibrinous  or  purulent 
character.  Beneath  the  membrane  the  tissue  is  hyperemic  and 
there  may  be  considerable  exudation  of  a  serous,  fibrinous  or 
haemorrhagic  character.  There  may  be  extensive  necrosis  of  the 
glands  or  of  the  muscular  tissue  in  the  vicinity.  The  membrane 
may  extend  from  the  throat  into  the  nose,  into  the  Eustachian  tube 
and  middle  ear.  Other  organisms,  chiefly  streptococci  and  staphyl- 
ococci,  may  be  found  in  large  numbers  in  the  membrane  often 
exceeding  the  diphtheria  bacilli  in  number.  In  fatal  cases  the 
lungs  are  almost  invariably  affected.  The  local  infection  may 
extend  from  the  throat  into  the  trachea  and  into  the  large  and 
small  bronchi  producing  a  similar  formation  of  membrane.  The 
most  common  lesions  found  in  the  lung  are  areas  of  exudation  into 
the  bronchi  and  connecting  air  sacs.  These  areas  vary  in  size  from 
those  just  visible  to  those  several  centimeters  in  diameter  and  are 
more  frequently  seen  in  the  inferior  and  posterior  parts  of  the  lung. 
The  exudate  is  composed  in  most  cases  of  fibrin,  or  it  may  be  puru- 
lent or  haemorrhagic.  Such  foci  of  lung  infection  begin  in  the  atria 
and  from  there  extend  into  the  air  sacs.  The  larger  areas  are  due, 
not  to  extension  of  the  infection  by  continuity,  but  by  infection  of 
all  of  the  terminal  lobules  of  a  single  bronchial  territory.  The 
organisms  producing  these  lesions  of  the  lung  may  be  diphtheria 
bacilli,  streptococci,  pneumococci  and  staphylococci,  alone  or  in 
combination  with  one  another.  The  cervical  lymph  nodes  are 
enlarged,  congested  and  softer  than  normal.  All  of  the  lymphoid 
tissue  in  the  body  is  affected  to  a  greater  or  less  degree.  The  lymph 
sinuses  are  all  enlarged  and  contain  numbers  of  phagocytic  endo- 
thelial  cells  and  leucocytes.  The  cells  in  the  germinal  centres 
undergo  necrosis  and  are  replaced  by  large  endothelial  cells.  The 
kidneys  are  nearly  always  fatty  and  the  lesions  are  chiefly  degen- 
erative in  character.  In  about  one-fourth  of  the  cases  there  is  a 
condition  known  as  acute  interstitial  nonsuppurative  nephropathy. 


292  PATHOLOGY 

This  consists  in  the  presence  of  foci  in  the  interstitial  tissue  which 
are  composed  principally  of  plasma  cells.  In  a  smaller  number  of 
cases  acute  lesions  of  glomeruli  are  found.  Degenerative  changes 
are  found  in  the  heart,  in  the  liver  and  in  the  nerves.  The  symp- 
toms of  the  disease  are  referable  rather  to  the  action  of  toxins 
produced  by  the  bacilli  than  to  the  local  lesions  associated  with 
their  presence,  except  where  local  obstruction,  as  in  the  larynx,  may 
lead  to  death  from  suffocation. 

A  CASE  OP  DIPHTHERIA 

Anatomical  Diagnoses.  Diphtheria  with  membrane  formation  in 
pharynx,  larynx,  trachea  and  bronchi;  Tracheotomy;  Broncho- 
pneumonia;  Acute  parenchymatous  degeneration;  Streptococcus 
infection. 

White,  male,  age  seven  years.  Body  that  of  a  fairly  well-developed 
and  fairly  well-nourished  boy.  Lividity  of  posterior  portions  of  the  body, 
no  oedema,  no  rigor  mortis.  An  open  wound  hi  the  anterior  middle  line 
of  the  neck  extending  into  the  trachea.  Subcutaneous  fat  small  in 
amount. 

Peritoneal  surface  smooth  and  glistening,  intestines  moderately 
distended. 

Pleural  cavities  free  from  exudate  or  adhesions. 

Pericardium  and  heart  normal. 

The  organs  of  the  neck  with  the  lungs  removed  in  mass.  The  oesopha- 
gus opened  posteriorly.  The  mucous  membrane  of  the  mouth  and 
pharynx  intensely  injected.  On  the  right  side  covering  the  tonsil  and 
extending  to  the  pillars  of  the  uvula  and  over  the  base  of  the  tongue  is  a 
dirty  brown  or  gray  adherent  membrane,  not  easily  removed,  coming 
away  in  small  patches.  The  surface  beneath  is  injected  and  rough. 
The  membrane  extends  deeply  into  the  crypts  of  the  tonsil  which  is 
swollen  and  haemorrhagic.  On  the  left  side  over  the  swollen  tonsil  is  a 
similar  but  less  extensive  membrane.  The  edges  of  the  membrane  are 
irregular.  The  trachea  and  larynx  opened  posteriorly.  Beginning  at 
the  base  of  the  epiglottis  and  extending  throughout  the  larynx,  trachea 
and  large  bronchi,  there  is  a  membranous  exudate,  white,  soft,  fragile, 
which  can  easily  be  stripped  from  the  underlying  deeply  injected  surface. 
There  is  an  incision  corresponding  to  the  external  wound  which  passes 
through  the  lower  portion  of  the  cricoid  cartilage  and  the  first  and  second 
rings  of  the  trachea.  The  lymph  nodes  of  the  neck  are  enlarged,  injected 
and  soft. 


BACILLUS   DIPHTHERLE  293 

The  lungs  collapse  but  slightly,  the  pleurae  are  smooth,  the  surface 
mottled  with  red  areas.  On  palpation  there  are  distinctly  perceptible 
smaller  and  larger  firm  areas.  On  section  the  lungs  are  hyperaemic  and 
cedematous.  Considerable  blood  and  air-containing  fluid  escapes  from 
incision.  There  are  areas  of  consolidation  from  0.5  to  1.5  cm.  in  diam- 
eter, some  of  these  red,  others  dark,  resembling  infarcts.  They  are  more 
numerous  in  the  lower  and  posterior  portions  of  the  lungs,  but  the  largest 
is  in  the  upper  lobe  of  the  right  lung.  From  some  of  the  areas  small 
drops  of  pus  exude  on  pressure. 

Spleen,  enlarged,  weight  165  grams.  Capsule  smooth.  On  section 
a  deep  red  color,  the  markings  obscure. 

Pancreas  and  adrenals  negative. 

Liver,  weight,  690  grams.  Surface  smooth,  mottled  with  red  and 
yellow  areas. 

Kidneys,  weight,  135  grams.  Capsule  easily  stripped,  the  surface 
smooth,  fcetal  markings  visible,  cortex  pale.  Pyramids  injected,  mark- 
ings obscure. 

Genitalia,  arteries  and  brain  present  no  lesions.  The  middle  ears 
normal. 

Cultures  from  lungs  show  streptococci  and  diphtheria  bacilli.  No 
histological  examination. 

REMARKS.  A  typical  case  of  severe  diphtheria  with  secondary 
streptococcus  infection.  The  character  of  membrane  in  pharynx 
and  in  trachea  is  characteristic.  In  the  trachea  easily  removed, 
soft  and  easily  torn;  in  the  pharynx,  the  squamous  epithelium  of 
which  enters  into  the  membrane  formation,  tough,  adherent.  The 
congestion  and  haemorrhage  in  the  underlying  tissue  is  also  charac- 
teristic. The  broncho-pneumonia  is  an  invariable  accompaniment 
of  a  diphtheria  infection  of  this  degree  of  severity  and  extension. 
The  swelling  of  spleen  and  kidneys  is  due  to  acute  degeneration 
brought  about  by  the  toxin.  Histological  examination  shows 
necrosis  in  the  lymphoid  tissues. 


INFLUENZA  BACILLUS 

This  is  an  extremely  small  bacillus  0.5/1  long  by  0.2-0.3  M  broad, 
not  motile,  does  not  stain  with  Gram  and  produces  no  spores.  It 
is  cultivated  with  difficulty,  haemoglobin  being  necessary  for  its 
growth.  It  is  not  fatal  for  laboratory  animals  but  intravenous 
injections  in  rabbits  exert  a  toxic  effect. 

In  man  the  organism  occurs  in  a  variety  of  pathological  condi- 
tions, either  alone  or  in  association  with  other,  and  for  the  most 
part  pyogenic,  organisms.  In  cases  of  death  from  epidemic  in- 
fluenza the  mucous  membrane  of  the  small  bronchi  is  injected  and 
covered  with  a  muco-purulent  exudate  in  which  are  great  numbers 
of  the  bacilli.  In  addition  to  the  bronchitis  there  may  be  extensive 
broncho-pneumonia,  in  the  exudate  of  which  the  bacilli  are  found 
both  free  and  enclosed  in  polynuclear  cells.  Cases  of  meningitis 
due  to  the  influenza  bacilli  may  occur  both  in  the  course  of  epidemics 
and  sporadically.  It  also  is  frequently  found  in  tuberculosis  and 
other  infections  of  the  lung.  In  view  of  the  frequency  of  the 
organism  it  is  difficult  to  regard  it  as  the  essential  cause  of  the 
great  pandemics  of  influenza. 


294 


TETANUS   BACILLUS 

This  is  a  long  slender  organism  possessing  many  flagellae.  It 
stains  with  usual  bacterial  stains  and  is  Gram  positive.  It  is  a 
strict  anaerobe  and  forms  spores  readily.  It  is  found  hi  cultivated 
earth  and  is  a  frequent  if  not  constant  inhabitant  of  the  alimentary 
canal  of  horses.  In  cultures  it  forms  a  toxin  to  which  its  pathogenic 
action  is  due.  Of  all  animals  the  horse  is  most  susceptible  to  the 
action  of  the  toxin.  In  man  the  disease  is  transmitted  by  wound 
infection.  The  inclusion  of  foreign  bodies  contaminated  with 
bacilli  in  penetrating  wounds  favors  infection,  the  bacilli  finding 
favorable  opportunity  for  development  in  the  necrotic  tissue 
around  the  foreign  body.  This  type  of  wound  tends  to  close  on 
the  surface  thus  providing  an  anaerobic  culture  medium. 

Mixed  infection  may  favor  the  development  of  the  bacilli.  The 
bacilli  produce  but  slight  local  reaction  of  the  tissue.  The  growth 
of  the  bacilli  in  the  tissue  is  feeble,  and  their  detection  difficult. 
The  infection  atrium  may  be  difficult  to  detect  at  the  time  when 
the  effects  of  the  toxin  appear. 


295 


BACILLUS  PESTIS 

This  is  a  very  short  bacillus  with  rounded  ends  without  motion, 
does  not  stain  with  Gram,  forms  no  spores,  retains  vitality  in  dark- 
ness and  in  moist  environment,  grows  readily  upon  meat  infusion 
and  at  low  temperatures.  The  organism  is  extremely  pathogenic 
for  the  laboratory  animals,  particularly  guinea  pigs  and  rats,  in 
which  the  mere  rubbing  of  a  culture  on  the  unbroken  skin  is  suffi- 
cient to  convey  invariably  fatal  infection.  Man  is  very  susceptible 
to  the  disease,  infection  taking  place  both  by  the  skin  and  respira- 
tory surface,  the  latter  giving  rise  to  the  pneumonic  form  of  the 
disease.  Infection  by  the  skin  can  take  place  through  surface 
lesions,  but  the  most  common  mode  of  infection  is  by  the  bites  of 
fleas  which  convey  the  bacilli  from  infected  rats.  The  bacilli,  in 
great  numbers,  are  found  in  the  lymph  nodes,  in  the  spleen,  in  the 
liver,  and  in  the  blood.  A  common  lesion  in  death  from  plague  is 
the  presence  of  hyalin  thrombi  in  the  glomerular  capillaries. 


2Q6 


BACILLUS    OF    SOFT    CHANCRE 

This  is  a  thick,  short  bacillus  with  round  ends,  having  a  tendency 
to  form  chains,  non-motile,  does  not  stain  with  Gram  and  does  not 
grow  on  ordinary  media.  Infection  in  man  takes  place  by  coitus, 
the  lesion  appears  on  the  genitals  as  an  ulcer  with  sharply  cut  edges 
and  a  base  covered  with  thin  purulent  and  haemorrhagic  exudation. 
The  edges  are  soft,  there  is  always  lymphangitis  with  inflammatory 
swelling  and  frequently  suppuration  of  the  adjacent  lymph  nodes. 


297 


BACILLUS   TYPHOSUS 

This  is  a  short,  actively  motile  bacillus,  having  twelve  or  more 
flagella  peripherally  arranged.  It  is  easily  cultivated  upon  the 
usual  laboratory  media.  It  grows  best  at  37.5°  C.,  but  also  grows 
between  15  and  41°  C.  It  is  capable  of  both  parasitic  and  sapro- 
phytic  growth. 

Infection  takes  place  from  the  alimentary  canal,  but  the  site  and 
the  mode  of  infection  are  obscure.  The  lesions  of  the  disease  are 
most  apparent  in  the  lymphoid  tissue  of  the  alimentary  canal  and 
this  has  led  to  the  view  that  the  organisms  enter  the  alimentary 
canal,  multiply  there  and  produce  the  lesions  which  constitute  the 
focus  of  infection  through  which  the  further  invasion  of  the  body 
takes  place.  The  process  of  infection  seems  to  be  that  the  bacilli 
enter  the  blood  from  the  alimentary  canal,  possibly  through  an 
intact  surface.  During  the  somewhat  indefinite  period  of  incuba- 
tion the  bacilli  multiply  in  the  blood,  and  the  characteristic  lesions 
in  the  lymphoid  tissue  of  the  alimentary  canal  and  elsewhere  are 
due  to  the  specific  action  of  the  bacilli  and  toxins  on  this  tissue. 
The  character  of  the  lesions  in  the  alimentary  canal  is  due  to  the 
situation  of  the  lymphoid  tissue  which  facilitates  surface  necrosis 
and  ulceration.  The  mode  of  action  of  the  bacilli  also  is  obscure. 
There  seems  to  be  little  or  no  definite  toxin  produced  in  culture,  but 
endotoxins  have  been  obtained  from  the  bodies  of  the  bacteria.  In 
the  tissues  the  bacilli  occur  in  groups  in  association  with  the  lesions, 
and  are  not  found  within  the  cells.  The  fresher  the  autopsy,  as  a 
rule,  the  smaller  the  number  of  organisms  which  will  be  found. 
Growth  of  the  single  bacilli  in  the  tissues  takes  place  after  death, 
resulting  in  the  formation  of  the  small  clumps.  The  characteristic 
feature  of  the  disease  is  the  production,  in  enormous  numbers,  of 
large  endothelial  cells  which  have  marked  phagocytic  properties  for 
lymphoid  cells,  but  not  for  bacilli.  These  cells  are  formed  from 
the  endothelium  in  various  places,  but  principally  from  the  lining 
cells  of  the  lymph  sinuses  and  from  the  endothelium  of  the  blood 
sinuses  of  the  spleen.  There  is  probably  also  some  increase  in  the 

298 


BACILLUS  TYPHOSUS  299 

number  of  lymphoid  cells,  but  relative  to  the  endothelial  cells  they 
are  few  in  number.  There  is  but  little  association  of  polynuclear 
leucocytes  with  the  lesions,  there  is  no  leucocytosis,  the  bacilli  have 
no  positive  chemotaxis  for  polynuclear  cells  and  these  only  appear 
in  the  lesions  hi  association  with  necrosis.  In  the  lesions  it  seems 
as  though  the  organisms  are  only  accidentally  present;  they  pro- 
duce no  necrosis  and  the  lesions  are  not  more  marked  hi  their  im- 
mediate vicinity.  While  this  is  the  characteristic  action  of  the 
typhoid  bacilli,  foci  of  suppuration,  particularly  in  the  periosteum, 
may  appear  during  the  latter  weeks  of  the  disease,  or  even  months 
after  convalescence.  Subcutaneous  abscesses  and  abscesses  deeply 
seated  in  the  muscles  have  been  described.  Meningitis  may  be 
produced  by  the  bacilli  and  occurs  late  hi  the  disease  or  during 
convalescence.  The  bacilli  find  their  way  into  the  gall  bladder 
from  the  blood;  they  are  found  there  early  in  the  disease  and  may 
remain  for  months  and  years  after  recovery.  The  bacilli  also  may 
appear  in  the  urine  during  the  course  of  the  disease,  entering  this 
from  small  lesions  in  the  kidneys.  They  always  are  present  in  the 
rose  spots  of  the  skin.  These  are  small,  flat,  slightly  elevated 
maculo-papules  surrounded  by  an  area  of  hyperaemia.  Histologi- 
cally  there  is  swelling  and  oedema  of  the  papillae  and  a  slight 
increase  in  the  tissue  cells. 


A  CASE  OF  TYPHOID  FEVER 

Anatomical  Diagnoses.  Typhoid  fever  hi  stage  of  beginning 
necrosis  and  ulceration;  Acute  swelling  of  spleen;  Acute  degene- 
ration of  heart,  liver  and  kidneys;  Pressure  decubitus  of  pharynx; 
(Edema  of  lungs. 

Female,  white,  age  twenty  years.  Death  occurred  on  the  tenth  day  of 
the  disease.  Autopsy  ten  hours  post  mortem. 

Body  of  medium  size,  well  nourished.  No  rigor  mortis.  Post-mortem 
lividity  marked.  Abdomen  prominent.  Subcutaneous  fat  in  moderate 
amount,  muscles  pale.  Peritoneum  smooth,  free  from  adhesions,  the 
spleen  large,  dark  red,  the  small  intestines  distended.  Diaphragm  right 
side,  fourth  interspace;  left,  fourth  rib. 

Right  pleural  cavity  free  from  adhesions.  A  few  long  fibrous  adhesions 
over  upper  lobe  of  left  lung.  Pleurae  otherwise  smooth,  moist  and  glis- 
tening. 


300  PATHOLOGY 

Pericardium  normal.  Heart  weight  260  grams.  Valves  normal. 
Myocardium  lax  and  pale.  Coronary  arteries  normal. 

Both  lungs  present  the  same  character.  There  is  but  little  pigment; 
they  are  pale  anteriorly,  the  posterior  and  inferior  portions  congested, 
heavy  and  cedematous.  On  section  of  these  parts  an  abundant  fluid 
mixed  with  air  can  be  expressed.  No  part  sinks  in  water. 

Gastro-intestinal  canal.  Stomach  contains  a  small  amount  of  fluid 
mixed  with  food  residue.  Mucous  membrane  rather  pale.  Duodenum 
and  upper  jejunum  are  normal.  Commencing  at  ileum  all  of  the  lym- 
phatic apparatus  of  the  intestine  is  swollen.  The  changes  are  more 
marked  as  the  caecum  is  approached.  Commencing  at  the  ileo-caecal 
valve  and  involving  the  edge  of  the  valve  is  a  large  swollen  area  10  cm. 
long  and  involving  almost  the  circumference  of  the  bowel.  The  surface 
of  this  area  is  irregular,  with  elevations  and  depressions,  the  color  gray. 
In  various  places  on  the  surface  are  opaque  gray-yellow  areas  from  0.5 
to  1.5  cm.  in  diameter  and  with  sharp  edges.  On  section  the  swollen 
area  varies  from  3  to  5  mm.  in  thickness.  The  differentiation  of  the  sub- 
mucous  and  muscular  coats  is  obscure  and  the  gray  swelling  extends  into 
the  muscularis.  On  scraping  the  section  with  a  knife,  a  thick  opaque 
fluid  is  obtained;  on  compression  the  swelling  breaks  down  into  a  soft 
mass. 

Peritoneum  over  the  area  is  smooth.  Extending  from  this  upwards 
a  similar  change  is  found  in  all  the  Peyer's  patches  and  solitary  follicles. 
The  edges  of  the  swollen  areas  are  sharp  and  spring  from  the  surface 
without  intermediate  grades.  On  several  of  the  Peyer's  patches  the 
same  yellow,  opaque  patches  on  the  surface  are  seen  and  in  one,  near  the 
large  swelling  described,  the  entire  surface  is  of  this  character.  The 
swellings  corresponding  to  the  solitary  follicles  are  from  2  to  5  mm.  in 
diameter  and  in  places  are  confluent.  In  several  of  them  there  are  small 
central  depressions.  The  bowel  contains  a  small  amount  of  yellow,  thin, 
fecal  material.  The  appendix  shows  much  the  same  condition  as  the 
ileum.  It  is  swollen,  somewhat  congested,  and  on  opening  it  there  is 
a  large  gray-pink  swelling  of  the  mucous  membrane  extending  over  the 
entire  proximal  end  for  a  distance  of  2.5  cm.  Beyond  this  there  are 
larger  and  smaller  swollen  areas.  The  ascending  and  the  transverse  colon 
are  thickly  strewn  with  small  circumscribed  elevations  of  the  same 
general  character  as  those  in  the  ileum,  which  correspond  with  the  soli- 
tary follicles.  They  are  less  numerous  in  the  descending  colon. 

All  the  mesenteric  lymph  nodes  and  those  in  the  mesocolon  are  swollen, 
the  single  nodes  often  confluent.  In  the  mesentery  4  cm.  from  the  valve 
is  a  large  node  4  by  2.5  by  2  cm.  in  size.  All  these  nodes  have  about  the 
same  character.  On  section  they  are  homogeneous,  rather  opaque,  of  a 


BACILLUS  TYPHOSUS  301 

gray  color,  soft,  some  of  them  almost  diffluent.    The  post-mesenteric 
nodes  also  enlarged,  but  not  to  the  same  extent. 

Spleen  large,  weight  630  grams,  the  anteroposterior  diameter,  par- 
ticularly, increased.  Surface  smooth,  the  capsule  tense.  On  section, 
of  a  homogeneous  rather  dark  red  color,  neither  trabeculae  nor  follicles 
visible,  the  interior  bulges  at  the  section.  Consistency  soft,  an  abundant 
red  pulp  obtained  on  scraping. 

Liver,  weight  1760  grams.  The  capsule  smooth,  the  surface  rather 
pale,  more  opaque.  Both  on  surface  and  on  section  the  lobular  markings 
are  obscure,  blood  contents  not  increased.  The  gall  bladder  of  normal 
size,  contains  a  small  amount  of  dark  fluid  bile,  the  wall  smooth. 

Pancreas  and  adrenal  glands  normal. 

The  kidneys,  weight  together  305  grams.  Capsule  easily  stripped, 
surface  smooth,  rather  pale  and  opaque.  On  section  cortex  well  dif- 
ferentiated from  pyramids,  6  by  8  mm.  in  thickness,  cortical  markings 
obscure,  glomeruli  not  visible.  Bladder  contains  about  500  c.c.  of  clear 
urine. 

Vagina,  uterus  and  ovaries  normal. 

Mucous  membrane  of  mouth  normal.  The  surface  of  tongue  dry  and 
brown.  The  tonsils  slightly  enlarged.  On  the  posterior  pharynx  wall 
corresponding  to  the  position  of  the  cricoid  cartilage  of  larynx  is  a  small 
transversely  situated  erosion  of  the  mucous  membrane  \  by  i^  cm.  in 
size.  Larynx  and  trachea  normal.  Thyroid  normal.  Section  of  femur 
shows  an  increase  in  red  marrow  and  in  this  there  are  circumscribed 
paler  foci. 

Cultures  from  the  spleen,  lymph  nodes,  liver,  bile  and  blood  gave  an 
abundant  growth  of  bacillus  typhosus  in  pure  culture. 

Microscopical  examination.  Section  through  one  of  the  swollen 
Peyer's  patches  shows  on  the  surface  the  epithelial  layer  in  places  absent 
and  replaced  by  necrotic  tissue  which  extends  a  varying  distance  into 
tissue  beneath.  At  the  border  of  the  necrosis  there  is  a  line  of  leucocytic 
infiltration.  In  the  general  mass  of  the  swelling  the  relations  of  the 
lymphoid  tissue  cannot  be  made  out.  There  are  areas  and  a  general 
infiltration  with  lymphoid  cells,  but  the  mass  of  swollen  tissue  is  com- 
posed of  large  cells  with  definite  outline,  having  a  thin  non-granular  cyto- 
plasm, a  vesicular  oval  or  curved  nucleus  containing  but  little  chromatin. 
These  cells  contain  numerous  lymphoid  cells  enclosed  in  vacuoles.  The 
enclosed  cells  are  variously  altered,  the  nuclei  converted  into  homo- 
geneous chromatin  masses  or  only  chromatin  fragments  remaining. 
Some  of  the  large  cells  contain  as  many  as  ten  lymphoid  cells.  The 
large  cells  seem  to  be  massed  in  areas  corresponding  with  lymphatics 
or  lymph  sinuses.  A  small  amount  of  fibrin  is  contained  between  the 


302  PATHOLOGY 

cells.  The  blood  vessels  are  not  generally  apparent.  The  condition 
extends  throughout  the  submucosa  and  along  the  vascular  tracts  through 
the  circular  muscle  coat  and  to  a  slighter  extent  through  the  longitudinal 
coat  and  beneath  the  peritoneum.  The  lymph  nodes  show  about  the 
same  condition. 

The  spleen  is  hyperaemic  and  shows  areas  of  haemorrhage.  There  are 
everywhere  both  within  the  sinuses  and  without,  large  endothelial  cells 
of  the  same  character  as  those  in  the  intestine,  but  larger  and  containing 
great  numbers  of  red  blood  corpuscles  which  show  various  stages  of  dis- 
integration. In  many  of  the  cells  there  are  masses  of  yellow  pigment 
granules.  The  follicles  are  not  increased  in  size  and  about  them  and  in 
their  interior  are  large  endothelial  cells  in  active  phagocytosis. 

The  liver  cells  are  slightly  swollen  and  granular.  In  the  capillaries 
everywhere  are  the  large  phagocytic  cells.  In  addition  to  this  general 
distribution  there  are  foci  which  are  composed  of  these  cells,  often  with 
strands  of  fibrin  between  them.  Within  some  of  these  foci  necrotic  liver 
cells  can  be  distinguished;  others  are  composed  of  the  endothelial  cells 
alone. 

Sections  of  the  heart  after  staining  with  Scharlach  R.  show  a  diffuse 
formation  of  very  fine  fat  granules  within  the  fibres. 

Sections  of  the  kidney  show  swelling,  vacuolation  and  irregular  granu- 
lation of  the  cells  of  the  convoluted  tubules.  The  glomeruli  are  normal. 
Granular  masses  are  found  in  the  lumina  and  casts  in  the  Henle  and 
collecting  tubules. 

REMARKS.  This  is  a  typical  case  of  typhoid,  in  which  the  most 
striking  lesion  is  the  infiltration  with  endothelial  phagocytic  cells. 
We  must  assume  that  their  proliferation  is  in  some  way  brought 
about  by  the  bacilli.  It  may  be  due  to  the  action  of  a  possible 
endotoxin  stimulating  the  cells,  or  some  substance  arising  from  the 
combined  action  of  the  bacilli  and  tissue  cells.  Usually  we  can  see 
or  fancy  we  see  some  purpose  connected  with  the  tissue  changes, 
but  in  this  case  no  such  purpose  is  apparent.  The  very  marked 
phagocytosis  for  the  lymphoid  cells  might  be  thought  an  attempt 
to  restore  the  cell  balance  broken  by  an  increased  formation  of 
lymphoid  cells,  but  there  is  no  evidence  of  this,  and  in  the  spleen 
they  devour  as  actively  the  red  blood  corpuscles. 


BACILLUS   TYPHOSUS  303 


A  CASE  or  TYPHOID  FEVER  WITH  PERFORATION  AND  ACUTE 
PERITONITIS 

(Only  those  portions  of  the  autopsy  protocol  which  refer  to  the  lesions 

are  used) 

Anatomical  Diagnoses.  Typhoid  fever;  Ulceration  of  ileum  with 
perforation;  Ulceration  of  colon;  Acute  peritonitis;  Acute 
splenic  tumor;  Acute  conjunctivitis. 

White  male,  age  forty-two  years.  Autopsy  eighteen  hours  post 
mortem.  Body  well  developed  and  fairly  well  nourished.  Rigor  mortis 
is  present.  There  is  lividity  of  the  dependent  parts.  Pupils  are  un- 
equal; right  4  mm.,  left  8  mm.  There  is  no  oedema.  The  right  con- 
junctiva is  considerably  injected  and  there  is  a  thin,  yellowish  fluid  in  the 
conjunctival  sac.  Abdomen  is  considerably  distended. 

Peritoneal  cavity.  On  opening  this,  there  is  a  considerable  escape  of 
gas  and  the  wall  collapses.  It  contains  200  c.c.  of  thin,  cloudy  fluid, 
containing  fibrin.  The  blood  vessels  of  the  omentum,  mesentery  and 
intestines  are  deeply  injected.  The  transverse  and  descending  colon 
are  markedly  distended  with  gas.  There  is  acute  inflammation  of  the 
peritoneum,  most  marked  over  the  lower  metre  of  the  small  intestine. 
The  appendix  measures  7  cm.  in  length,  has  a  mesentery  to  tip  and  no 
adhesions.  Its  mucosa  is  normal.  The  mesenteric  lymph  nodes  are 
considerably  increased  in  size,  rather  soft  in  consistence,  and  on  section 
are  dark  red  in  color.  Diaphragm  normal  in  position. 

Spleen.  Weight  240  grams.  The  surface  is  smooth.  Capsule  is 
rather  tense.  On  section  the  pulp  bulges  somewhat  beyond  the  capsule. 
A  large  amount  of  blood  escapes.  The  pulp  is  quite  soft  and  semi- 
diffluent.  The  general  color  is  dark  red.  Malpighian  bodies  are  not 
apparent. 

Gastro-intestinal  tract.  The  peritoneal  covering  shows  acute  inflam- 
mation. Throughout  the  lower  metre  of  the  small  intestine,  situated 
opposite  the  mesenteric  attachment,  are  several  sharply  outlined,  dark 
red  areas,  visible  through  the  peritoneum.  Some  are  almost  black. 
Their  general  direction  is  with  the  long  axis  of  the  ^intestine.  Four 
centimeters  from  the  caecum  there  is  a  perforation  through  the  intestinal 
wall ;  the  edges  of  this  opening  are  thickened,  everted  and  covered  with 
fibrin.  About  the  opening  the  tissue  is  deeply  injected.  The  perfora- 
tion is  opposite  the  mesentery  in  the  central  portion  of  an  oblong,  dark 
red  area.  On  opening  the  intestine  this  perforation  is  in  the  centre  of  a 
deep  ulcer.  There  are  twenty  ulcers  in  the  lower  metre  of  the  small 


304  PATHOLOGY 

intestine.  They  vary  in  size,  shape  and  depth.  The  largest  is  2.5  by 
2  cm. ;  the  smallest  8  mm.  The  larger  ulcers  are  deep  and  shaggy;  some 
involve  all  of  the  intestinal  wall,  their  base  being  formed  by  the  peri- 
toneum. The  smaller  ones  are  not  so  deep.  Generally  all  have  elevated 
and  thickened  edges  and  are  covered  with  a  purulent  exudate.  In  the 
caecum  and  upper  20  cm.  of  the  colon  are  several  ulcers,  generally  round 
to  oval,  of  the  same  general  character  as  those  in  the  ileum,  although 
smaller.  On  the  posterior  portion  of  the  ascending  colon,  8  cm.  from  the 
tip  of  the  caecum  is  an  irregularly  shaped,  ulcerated  area  10  by  8  mm.  It 
is  quite  sharply  outlined.  The  base  of  this  ulcerated  area  is  made  up 
of  external  muscular  coat  of  the  intestine. 

REMARKS.  The  condition  is  self-explanatory.  The  term  "acute 
splenic  tumor"  refers  merely  to  the  acute  swelling  of  the  spleen, 
which  is  so  characteristic  a  feature  of  the  disease. 


BACILLUS   DYSENTERIC 

This  is  a  short  rod  very  similar  morphologically  to  the  typhoid 
and  to  the  colon  bacillus.  It  produces  no  spores,  is  easily  culti- 
vated, and  does  not  stain  by  the  Gram  method.  Study  of  the 
organism  has  shown  that  there  are  several  species  or  strains  all  of 
which  exert  similar  pathogenic  action.  In  rabbits  the  intravenous 
injection  of  the  organism  causes  a  violent  diarrhoea  with  acute 
inflammation  of  the  colon.  Infection  in  man  probably  takes  place 
in  the  alimentary  canal.  The  lesions  produced  in  man  by  the 
organism  are  in  the  large  intestine  and  they  vary  greatly  in  extent 
and  character.  The  essential  process  is  inflammation  of  the  mucous 
membrane  usually  leading  to  destruction  and  ulceration.  In  cer- 
tain cases  there  is  superficial  necrosis  with  the  formation  of  fibrinous 
exudation  on  the  surface  which  may  be  extensive  or  occur  in  small 
foci  (diphtheritic  dysentery).  The  exudation  is  most  marked  on 
the  surface  of  the  folds  of  mucous  membrane.  The  ulcers  may  be 
single  and  small,  or  numerous  and  extensive.  In  the  acute  summer 
dysentery  of  young  children,  the  intestinal  lesions  may  be  limited 
to  a  few  small  ulcers.  In  both  the  acute  and  chronic  forms  the 
mucous  membrane  may  be  destroyed  over  large  areas,  leaving 
elevated  islands  of  intact  surface.  There  is  nothing  characteristic 
in  the  appearance  of  the  ulcers.  Dysentery  as  produced  by  this 
organism  may  appear  sporadically  or  hi  epidemic  form. 

A  CASE  OF  ACUTE  EPIDEMIC  DYSENTERY  WITH  CHRONIC  MALARIA 

This  case  was  one  of  a  number  of  cases  which  occurred  during  an 
epidemic  of  dysentery  in  a  large  asylum.  The  disease  was  very  fatal, 
the  mortality  reaching  35  per  cent.  The  population  of  the  asylum  con- 
sisted largely  of  debilitated  anaemic  old  people  in  whom  the  greatest 
mortality  occurred. 

Anatomical  Diagnoses.  Acute  epidemic  dysentery;  Necrosis  and 
ulceration  of  colon  and  rectum;  Chronic  malaria;  Anaemia; 
Necrosis  of  liver;  Hyperplasia  of  lymph  nodes;  (Edema  of  lungs. 

3°S 


306  PATHOLOGY 

White  male,  age  sixteen  years.  The  body  of  ordinary  size,  emaciated, 
the  surface  pale  with  slight  icteric  tint.  Subcutaneous  fat  small  in 
amount;  the  muscles  pale. 

Peritoneum  smooth.  About  200  c.c.  of  clear  fluid  with  slight  yellow 
tint  in  the  cavity.  The  peritoneal  surface  of  the  colon  injected.  All 
the  lymph  nodes  in  the  meso-colon  enlarged  and  pale  red  in  color.  The 
mesenteric  and  post-peritoneal  nodes  slightly  enlarged. 

Pericardium  normal.  In  the  cavity  a  few  cubic  centimeters  of  clear, 
slightly  yellow  fluid. 

Heart  weight  270  grams.  Myocardium  pale  and  friable.  Endo- 
cardium and  valves  normal.  The  pleurae  free  from  adhesions,  the  fluid 
in  cavity  slightly  increased  in  amount. 

The  lungs.  The  surface  pale  with  carbon  tracings  along  the  pleural 
lymphatics.  On  section  considerable  fluid  mixed  with  air  exudes  from 
the  posterior  portions  of  each  lung.  The  mucous  membrane  of  bronchi 
pale. 

Liver  weight  1450  grams.  The  organ  a  pale  slate  color.  The  surface 
smooth.  On  section,  consistency  normal,  the  lobules  visible. 

The  spleen.  Large,  weight  235  grams.  The  surface  smooth,  the 
organ  of  a  deep  slate  color,  consistency  firm,  follicles  prominent  against 
the  dark  background.  On  scraping,  the  pigmented  pulp  comes  away. 

The  pancreas  normal. 

Intestinal  canal.  Mucous  membrane  of  stomach  and  upper  part  of 
small  intestine  pale.  The  follicles  and  Peyer's  patches  prominent.  For 
a  space  of  20  cm.  above  the  ileocaecal  valve  the  mucous  membrane  of 
ileum  is  swollen,  deeply  injected,  and  over  the  surface  there  are  pale, 
opaque  and  rather  dry  flecks  which  tend  to  occur  in  lines  transverse  to 
the  axis  of  the  gut.  In  places  there  are  small  foci  of  haemorrhage.  This 
condition  is  not  more  marked  over  the  Peyer's  patches  than  elsewhere. 
There  is  no  ulceration  save  on  the  surface  of  the  valve  where  there  are 
a  few  superficial  irregular  losses  of  substance.  The  mucous  membrane 
of  the  ascending  and  the  beginning  of  the  transverse  colon  is  swollen  and 
hyperaemic.  On  the  surface  there  are  a  few  scattered  pale,  opaque  flecks 
similar  to  those  described  in  the  ileum.  Commencing  in  the  middle  of 
the  transverse  colon  the  swelling  and  hyperaemia  of  the  mucous  mem- 
brane is  more  intense,  and  the  spots  of  exudation  on  the  surface  more 
numerous,  these  coalescing  in  places  to  form  a  dry  gray,  opaque  mem- 
brane which  is  firmly  adherent.  On  section  this  condition  in  places 
involves  the  entire  thickness  of  the  mucous  membrane;  in  places  it  is 
superficial.  It  is  more  marked  on  the  surfaces  of  elevations  than  else- 
where. The  scattered  flecks  are  so  sharply  circumscribed  as  to  present 
an  appearance  as  though  some  foreign  material  had  been  scattered  over 


BACILLUS  DYSENTERLE  307 

the  surface.  In  the  lower  portion  of  the  descending  colon  and  in  the 
upper  rectum  the  condition  gives  place  to  extensive  ulceration.  The 
ulcers  in  places  are  so  extensive  that  but  irregular  islands  of  mucous 
membrane  appear  on  the  surface.  The  ulcers  are  superficial  not  passing 
into  the  muscularis.  They  are  smooth  on  the  surface,  not  necrotic,  and 
the  base  is  red  and  granular.  The  smaller  ulcers  show  no  undermining; 
the  edges  are  sharp  and  of  irregular  shape.  The  ulceration  extends  to 
6  cm.  above  the  anus. 

Kidneys,  combined  weight,  270  grams.  Capsule  not  adherent,  the 
surface  smooth  rather  pale.  On  section  pale,  opaque;  the  markings  of 
cortex  accentuated;  the  pyramids  pale. 

Ureters,  bladder  and  urethra  normal. 

Neck  organs.  The  mucous  membrane  of  mouth  and  pharynx  pale; 
the  tonsils  slightly  enlarged.  The  mucous  membrane  of  larynx  and 
oesophagus  pale. 

Meninges  and  brain  present  no  lesions. 

Microscopic  examination.  A  marked  degree  of  fatty  degeneration  in 
myocardium  both  diffuse  and  focal.  It  is  most  marked  in  the  inter- 
ventricular  septum  and  at  the  bases  of  the  papillary  muscles  of  left 
ventricle. 

The  liver  contains  much  fat  in  the  cells  in  the  form  of  small  droplets 
irregularly  distributed.  Almost  everywhere  there  are  areas  of  necrosis 
around  the  central  veins  of  the  lobules  which  vary  in  size,  in  some 
of  the  larger  extending  to  the  middle  of  the  lobule.  In  most  places 
and  particularly  in  the  larger  areas  the  necrotic  cells  are  invaded  by  poly- 
nuclear  leucocytes.  In  the  sinuses  there  are  numbers  of  large  endothe- 
lial  cells  containing  black  pigment  hi  round  or  irregular  variously  sized 
granules.  In  places  the  pigment  is  contained  in  cells  of  the  same  char- 
acter but  which  are  attached  to  the  walls. 

The  spleen  shows  large  masses  of  pigment  which  in  part  is  within 
large  cells  similar  to  those  in  the  liver;  in  part  appear  to  be  free.  The 
follicles  are  enlarged  and  in  the  centres  of  many  of  these  there  is  much 
nuclear  detritus  and  among  this  large  pale  ovoid  nuclei.  Here  and  there 
the  cytoplasm  belonging  to  these  nuclei  can  be  distinguished,  and  con- 
tains much  of  the  free  nuclear  detritus. 

Sections  through  the  colon  involving  the  scattered  flecks  on  surface 
show  circumscribed  necrosis  of  mucous  membrane,  most  extensive  on 
the  surface.  There  is  much  haemorrhage  in  connection  with  this  and 
fibrinous  exudation,  the  necrosis  haemorrhage  and  exudation  combining 
to  form  lenticular  patches  which  extend  above  the  surface.  In  the 
splenic  flexure  the  necrosis  and  exudation  are  more  extensive  involving 
the  entire  mucous  membrane  but  in  no  place  extending  into  the  sub- 


308  PATHOLOGY 

mucosa.  In  this  the  blood  vessels  are  injected  and  contain  numerous 
leucocytes.  In  places  there  are  slight  haemorrhages  and  a  small  amount 
of  fibrinous  exudation  in  the  form  of  thin  fibrin  filaments.  There  is  a 
general  infiltration  of  cells,  in  large  part  small  lymphocytes,  more  marked 
around  the  veins.  There  are  also  a  number  of  endothelial  and  plasma 
cells.  In  the  ulcerated  areas  the  bases  of  the  ulcers  extend  in  places  to 
the  muscularis  but  usually  they  are  more  superficial. 

REMARKS.  This  is  a  typical  case  of  acute  epidemic  dysentery 
caused  by  the  bacillus  dysenteriae,  either  the  Shiga  or  Flexna  type. 
The  autopsy  was  made  in  1881  before  the  time  when  cultures  were 
customary.  In  the  institution  at  this  time  it  was  recognized  that 
there  were  two  anatomical  types  of  dysentery  but  no  etiological  dif- 
ferentiation could  be  made.  Compare  the  lesions  in  this  case  with 
those  of  amoebic  dysentery,  page  314.  Lesions  so  extensive  as  in 
this  case  are  not  usual.  In  young  children  there  may  be  focal 
hyperaemia  merely  or  a  few  superficial  ulcers. 


CHOLERA   SPIRILLUM 

This  is  a  small  slightly  curved  rod,  the  curve  in  the  three  dimen- 
sions of  space.  It  is  actively  motile,  has  a  single  polar  flagellum, 
does  not  stain  with  Gram  and  produces  no  spores.  It  grows  readily 
in  the  ordinary  culture  media,  the  temperature  limits  being  22- 
40°  C.  Alimentary  canal  infection  can  be  produced  in  animals 
after  neutralization  of  the  gastric  juice  with  sodium  carbonate,  and 
the  use  of  opium  to  prevent  active  peristalsis.  The  toxic  proper- 
ties of  the  organism  are  due  chiefly  to  endotoxins,  the  formation 
of  true  secretory  toxins  being  uncertain. 

Cholera  is  a  human  disease,  and  infection  takes  place  in  the  ali- 
mentary canal.  The  organisms  can  be  transmitted  by  contact, 
by  use  of  infected  articles  and  chiefly  by  the  contamination  of  water 
supplies.  The  organism  grows  in  the  alimentary  canal  and  pro- 
duces an  acute  inflammation  of  the  surface  with  destruction  and 
desquamation  of  the  epithelium.  The  organisms  are  present  in 
great  numbers,  but  there  is  no  tendency  to  invasion.  The  tissues 
are  dry  and  the  blood  rendered  more  viscid  owing  to  the  great 
amount  of  serous  exudation  poured  into  the  intestine. 


309 


BACILLUS   COLI   COMMUNIS 

This  is  a  short,  plump  organism,  a  constant  inhabitant  of  the 
alimentary  canal  of  man  and  of  other  warm-blooded  animals.  It 
grows  readily  in  most  culture  media  at  temperatures  between  20° 
and  40°;  it  is  not  an  exclusive  parasite;  it  is  provided  with  flagella, 
forms  no  spores  and  is  decolorized  in  the  Gram  stain.  It  is  slightly 
pathogenic  for  laboratory  animals.  The  virulence  of  different 
strains  of  the  bacillus  varies  greatly.  The  toxic  action  is  due  to 
endotoxins. 

Secondary  and  terminal  invasions  of  the  body  by  the  organism 
are  common.  In  almost  all  lesions  of  the  alimentary  canal,  how- 
ever produced,  colon  bacilli  are  found  hi  the  organs  on  culture. 
Pyelonephritis,  the  acute  inflammation  of  the  kidney  due  to  the 
extension  to  the  kidney  of  an  infectious  process  lower  down  in  the 
urinary  track,  very  frequently  is  produced  by  the  colon  bacilli. 
Cases  of  cholecystitis  and  cholangitis  and  associated  abscess  of  the 
liver  may  be  due  to  this  organism.  It  often  is  associated  with 
other  organisms  in  lesions  and  it  is  uncertain  hi  these  cases  what 
part  it  plays  in  their  production. 

A  CASE  OF  INFECTED  THROMBUS  OF  MESENTERIC  VEIN 

WITH  ABSCESSES  IN  THE  LIVER  ASSOCIATED  WITH 

COLON  BACILLUS 

Anatomical  Diagnoses.  Appendectomy;  Acute  peritonitis;  Puru- 
lent pylephlebitis  with  thrombosis;  Emboli  in  liver  with  multiple 
abscess  formation;  Jaundice;  Acute  hyperplasia  of  spleen;  Acute 
degeneration  of  kidneys. 

White,  male,  aged  fifty-two  years.  Two  years  previous  to  present 
illness  had  severe  pain  in  right  lower  quadrant  of  abdomen.  Present 
sickness  began  with  pain  in  same  region  which  rapidly  increased  in 
intensity  and  was  accompanied  by  vomiting  and  chills.  Blood  count 
showed  a  leucocytosis  of  29,200.  Tenderness  over  right  iliac  region. 
At  operation  the  appendix  was  found  swollen,  dark  colored  and  hard. 
On  tying  the  ligature  around  it  previous  to  excision,  it  was  torn  across 

310 


BACILLUS  COLI  COMMUNIS  311 

and  a  small  amount  of  the  contents  escaped  soiling  the  edges  of  the  wound. 
On  the  third  day  after  operation  marked  jaundice  developed  with  chills 
and  high  fever  followed  by  profuse  sweating.  A  blood  count  made  at 
this  time  showed  a  drop  in  the  leucocytosis  to  15,000.  The  rectal  tem- 
perature varied  between  102  and  106  degrees.  Death  on  the  fourth  day 
after  operation.  Incision  at  autopsy  limited  to  abdomen. 

Body  well  developed  and  well  nourished.  The  abdomen  distended. 
Rigor  mortis  of  legs.  Skin  everywhere  of  a  bright  yellowish  color. 
Conjunctivae  greenish  yellow.  In  the  abdominal  wall  in  the  region  of 
the  right  rectus  muscle  is  an  oval  wound  opening  into  the  abdominal 
cavity.  Subcutaneous  fat  in  fair  amount  and  greenish  yellow  in  color. 

The  omentum  is  firmly  adherent  to  the  edges  of  wound  and  to  the 
underlying  loops  of  the  intestine.  The  right  iliac  fossa  contains  10  c.c. 
of  thick,  creamy  pus  streaked  with  blood.  The  spleen  large  and  ad- 
herent by  soft  fibrinous  adhesions.  The  general  peritoneal  surface  is 
cloudy,  with  a  few  flocculi  of  fibrin  over  intestines.  The  small  intestines 
distended  with  gas. 

The  gall  bladder  is  distended,  its  ducts  free. '  The  portal  vein  and  its 
gastric  and  splenic  branches  free  from  clots.  The  superior  mesenteric 
vein  beginning  at  its  extremity  near  the  appendix  is  filled  with  a  firmly 
adherent  gray-red  thrombus.  The  wall  of  the  vein  is  distinctly  thick- 
ened and  soft.  The  clot  in  places  is  soft  and  purulent,  and  near  to  the 
opening  into  the  portal  vein  the  lumen  of  the  vein  contains  a  thick 
purulent  material. 

Beginning  at  the  entrance  of  the  portal  vein  into  the  liver  all  the 
portal  branches  contain  pus.  Throughout  the  liver  extending  in  the 
direction  of  the  portal  veins  are  numerous  abscess  cavities,  their  walls 
irregular,  due  to  the  union  of  contiguous  abscesses.  The  cavities  are 
surrounded  by  areas  of  necrotic  liver  tissue.  They  contain  a  thick 
greenish  yellow  pus.  Some  of  the  abscesses  are  near  the  surface  and 
separated  from  the  peritoneal  cavity  by  the  capsule  of  the  liver  only. 

Spleen,  weight,  340  grms.  Fibrinous  adhesions  chiefly  over  posterior 
surface.  On  section  soft,  edges  of  incision  bulging,  dark  red  in  color. 
Follicles  not  prominent. 

Pancreas  normal. 

Kidneys  weigh  315  grams.  Capsules  nonadherent.  Cortex  of  bright 
yellowish  red  color.  Markings  normal. 

Cultures  from  liver  abscesses  show  colon  bacilli  in  pure  culture. 

Sections  of  the  liver  show  abscesses  with  extensive  necrosis,  purulent 
infiltration  and  softening  in  surrounding  tissue.  In  places  branches  of 
the  portal  vein  are  found  filled  with  granular  material  containing  masses 
of  bacteria,  the  walls  necrotic  and  surrounded  by  necrotic  liver  tissue. 


312  PATHOLOGY 

The  portal  tissue  in  the  intact  areas  of  the  liver  is  infiltrated  with  lymph- 
oid  cells. 

The  spleen  shows  intense  hyperaemia  with  foci  of  haemorrhage.  The 
malpighian  bodies  are  not  enlarged. 

In  the  kidneys  there  is  cloudy  swelling,  fatty  degeneration,  with  here 
and  there  necrosis  and  desquamation  of  the  cells  of  the  convoluted 
tubules.  The  necrotic  cells  contain  bile  pigment,  and  deeply  pigmented 
hyalin  casts  are  found  chiefly  in  the  collecting  tubules. 

REMARKS.  A  recurrent  attack  of  appendicitis  of  a  severe  char- 
acter terminating  in  gangrene  of  the  appendix.  The  blood  count 
shows  an  acute  inflammatory  leucocytosis,  and  the  fall  in  the  num- 
ber of  leucocytes  after  the  operation  is  of  importance  in  showing  a 
lack  of  resistance.  The  acute  peritonitis  is  the  result  of  peritoneal 
infection  which  may  have  taken  place  at  the  time  of  operation  or 
preceding  this.  The  acute  phlebitis  with  thrombus  formation  is 
the  result  either  of  infection  of  the  vein  from  the  peritoneal  focus 
or  there  may  have  been  infection  of  a  small  branch  leading  from  the 
appendix.  In  either  case  there  was  extension  in  the  continuity  of 
the  vein.  The  thrombi,  so  formed,  underwent  purulent  softening 
and  gave  rise  to  numerous  infectious  emboli  which  were  carried  to 
the  liver  and  produced  the  abscesses.  The  jaundice  results  from 
occlusion  of  the  bile  ducts  by  the  abscesses.  The  acute  swelling 
of  the  spleen  is  the  consequence  of  congestion  due  to  the  occlusion 
of  the  hepatic  branches  of  the  portal  vein,  and  the  acute  degenera- 
tion of  the  kidneys,  which  is  a  constant  feature  in  acute  jaundice, 
is  due  to  the  action  of  the  bile  salts  on  the  epithelium. 


ENTAMGEBA  HISTOLYTICA 

Amoebic  dysentery  is  a  form  of  chronic  inflammation  of  the  large 
intestine  with  ulceration  caused  by  the  entamceba  histolytica. 
This  organism  is  from  15  to  25  n  in  diameter.  It  consists  of  a 
clear  hyalin  outside  area,  the  ectosarc,  surrounding  a  granular 
area,  the  entosarc,  which  contains  the  nucleus.  The  organism 
when  obtained  from  fresh  stools,  and  particularly  on  the  warm 
stage,  is  actively  amoeboid,  large  blunt  processes  of  the  ectosarc 
being  thrust  out  into  which  the  granular  entosarc  flows.  The 
amoebae  are  phagocytic  and  red  blood  corpuscles,  other  cells  and 
bacteria  often  are  within  them.  The  nucleus  is  single,  large  and 
vesicular  consisting  of  a  nuclear  membrane  from  the  internal 
surface  of  which  bits  of  chromatin  project.  In  sections  of  the 
intestine  the  amoebae  can  be  recognized  by  an  outer  membrane, 
seemingly  formed  by  the  contraction  of  the  ectosarc,  and  an  interior 
shrunken  mass  of  granular  cytoplasm.  The  intestinal  lesions  con- 
sist of  ulcers  which  are  greatly  undermined  and  often  connected 
by  sinuous  passages  in  the  submucosa.  The  submucosa  in  the 
vicinity  of  the  ulcers  is  swollen  by  an  cedamatous  and  fibrinous 
exudate.  The  amoebae  are  usually  most  abundant  where  the  under- 
mining of  the  mucous  membrane  is  advancing.  The  leucocyte 
reaction  is  slight;  the  cellular  infiltration  in  the  submucosa  consists 
of  lymphoid  and  endothelial  cells.  The  term  "histolytica"  de- 
scribes well  the  action  of  the  amoebae  in  producing  histolysis  of  the 
tissue  about  them.  The  intestinal  lesions  are  almost  characteristic 
but  in  rare  instances  ulcers  of  a  similar  type  may  be  found  hi 
chronic  bacterial  infection  of  the  intestine.  In  connection  with 
the  intestinal  lesions,  abscess  of  the  liver,  due  to  the  embolic  exten- 
sion of  the  amoebae  into  the  liver,  not  infrequently  are  found. 
Abscess  of  the  liver  may  also  be  produced  by  the  amoebae  extending 
directly  into  the  liver  from  the  hepatic  flexure  of  the  colon  which 
has  previously  become  adherent.  The  same  process  of  gradual 
liquefaction  of  tissue  takes  place  in  the  production  of  the  liver 
abscess,  as  in  the  extension  of  the  ulceration  in  the  submucosa  of  the 

313 


314  PATHOLOGY 

intestine.  Similar  conditions  may  be  caused  by  the  entamceba 
tetragena  but  the  entamoebacoli  is  a  nonpathogenic  inhabitant 
of  the  colon. 

A  CASE  OF  AMOEBIC  DYSENTERY  WITH  LIVER  ABSCESSES 

Anatomical  Diagnoses.  Multiple  amoebic  abscesses  of  liver;  Cir- 
cumscribed amoebic  peritonitis  from  perforation  of  liver  abscess; 
Operation  wound  into  abscess  of  liver;  General  fibrino-purulent 
peritonitis;  Amoebic  dysentery  with  perforation;  Emphysema 
of  lung;  Anthracosis  of  lung. 

The  body  that  of  a  man  about  fifty  years  old,  rather  small,  slightly 
built,  greatly  emaciated.  Body  length  171  cm. 

In  the  anterior  abdominal  wall,  in  the  median  line,  commencing  close 
beneath  the  ensiform  cartilage,  and  extending  downward  a  little  to  the 
right  side,  is  an  incision  6  cm.  long,  closed  by  fine  sutures.  Subcutaneous 
fat  slight  hi  amount.  Muscles  dark;  abdomen  retracted. 

Heart,  weight,  340  grams.  The  pericardium  hi  one  place  firmly  ad- 
herent. The  myocardium  rather  dark.  Valves  normal.  Coronary 
arteries  normal. 

Aorta  normal. 

Both  lungs  free  from  adhesions,  save  along  diaphragm,  where  there 
are  slight,  easily  broken-down  fibrinous  adhesions.  Both  lungs  in  high 
degree  emphysematous;  very  dark  in  color  from  coal  pigment.  Bronchi 
slightly  dilated,  pale;  otherwise  normal. 

Before  opening  abdomen  slight  induration  could  be  felt  in  left  hypo- 
chondrium.  On  opening  abdomen  the  incision  in  abdominal  wall  is 
found  to  pass  into  a  sac  on  the  lower  border  of  the  liver.  The  trans- 
verse colon  is  adherent  to  the  anterior  abdominal  wall,  shutting  off  the 
peritoneal  cavity  below.  The  small  intestines  are  slightly  adherent  to 
one  another,  and  in  places  between  the  folds,  and  especially  toward  the 
root  of  the  mesentery,  there  are  masses  of  gelatinous  looking  fibrin.  The 
same  gelatinous  looking  fibrin  extends  down  into  the  pelvis.  There  is 
an  abscess  cavity  which  extends  along  the  left  border  of  the  liver,  be- 
tween that,  the  colon,  the  stomach,  the  spleen  and  the  abdominal  wall. 
This  abscess  cavity  is  filled  with  a  gray,  more  or  less  tenacious,  fibrinous, 
gelatinous  pus.  Along  the  hepatic  side  of  the  transverse  colon  there  is 
an  abscess  communicating  with  the  first  abscess  by  a  small  opening,  and 
which  is  filled  with  a  yellowish  purulent  material.  There  are  several 
large  openings  from  the  transverse  colon  into  this  abscess.  All  of  the 
tissues  bordering  upon  the  abscess  appear  to  be  more  or  less  softened 
as  though  from  the  action  of  gastric  juice. 


ENTAMCEBA  HISTOLYTICA  315 

The  liver  is  not  enlarged.  On  the  anterior  lower  border  of  the  liver 
there  is  a  large  sac  which  extends  directly  into  the  liver,  and  which  is 
continuous  with  the  peritoneal  abscess.  This  sac  is  filled  with  a  thin 
yellowish  material.  Its  walls  are  deeply  stained  with  bile.  On  section 
of  the  wall  there  is  everywhere  a  hard,  fibrous  limiting  membrane.  In 
a  few  places  there  are  pockets  filled  with  the  gelatinous  pus  described 
before,  which  extend  from  the  abscess  wall  into  the  liver.  This  abscess 
cavity  measures  8  by  6  cm. 

On  cutting  into  the  liver  in  the  middle  of  the  right  lobe  there  is  an 
abscess  cavity  4  by  3  cm.  in  diameter.  This  presents  on  section  a  granu- 
lar reticular-looking  mass,  yellow  and  necrotic,  and  in  the  meshes  of  the 
reticulum  there  is  thick,  gelatinous  looking  pus.  This  abscess  cavity  is 
not  very  sharply  circumscribed,  but  the  necrotic  tissue  extends  directly 
into  the  liver.  On  the  upper  surface  of  the  liver,  between  that  and  the 
diaphragm,  there  are  fresh,  easily  broken-down  adhesions,  composed  of 
gelatinous  fibrin.  The  bile  ducts  are  dilated. 

The  spleen,  weight,  135  grams.  Dark;  its  capsule  wrinkled  and 
covered  with  a  gelatinous,  fibrinous,  purulent  mass.  The  spleen  forms 
part  of  the  abscess  cavity  first  described. 

The  mucous  membrane  of  stomach  somewhat  hyperaemic,  otherwise 
normal.  The  duodenum  normal. 

The  large  intestine  throughout  contains  numerous  ulcers.  Beginning 
at  the  caecum,  in  the  ascending  colon  the  mucous  membrane  is  swollen, 
thickened,  gelatinous,  and  here  and  there  in  it  there  are  small  circular 
undermined  ulcers,  the  largest  of  them  1.5  cm.  in  diameter,  with  gela- 
tinous purulent  infiltration  of  the  submucosa  extending  for  some  distance 
around  the  ulcer.  In  the  transverse  colon  the  lumen  is  dilated,  the 
mucous  membrane  is  thickened,  and  everywhere  there  are  large  ragged 
ulcers  covered  with  gangrenous  black  sloughs;  the  surrounding  mucous 
membrane,  where  it  is  preserved,  is  thickened;  the  submucosa  infiltrated. 
The  intestine  contains  a  yellow,  rather  thick,  more  or  less  viscid,  material. 
Several  deeper  ulcers  have  perforated  into  the  peritoneum. 

Kidneys.  Combined  weight  360  grams.  Capsule  strips  easily. 
Cortex  and  pyramids  normal.  Markings  somewhat  obscure. 

Adrenal  glands  and  pancreas  normal. 

Pelvic  contents  normal,  with  the  exception  of  rectum,  in  which  similar 
ulcers  to  those  in  the  ascending  and  descending  colon  are  found. 

The  microscopic  examination  of  the  contents  of  the  abscess  of  the  liver 
and  of  the  intestine  shows  large  numbers  of  vacuolated  amoebae,  hi  some 
instances  containing  red  blood  corpuscles.  Movement  could  be  made 
out  in  but  few  of  these.  Amoebae  also  were  found  in  the  gelatinous 
material  in  the  general  peritoneal  cavity. 


3i6  PATHOLOGY 

REMARKS.  This  autopsy  with  the  exception  of  the  peritoneal 
abscess  is  fairly  typical  of  amoebic  dysentery.  The  character  of 
the  lesions  in  the  colon  and  the  character  of  the  liver  abscesses  is 
indicative  of  amoebic  infection.  The  pus  in  the  liver  abscesses 
usually  contains  the  gelatinous  viscid  material  described  here.  In 
the  absence  of  continuity  with  the  intestine  from  perforation  they 
usually  contain  no  bacteria.  The  main  interest  in  the  case  apart 
from  the  amoebic  infection  is  in  the  peritoneal  abscess.  In  this 
region  of  the  peritoneal  cavity,  peritonitis  from  infection  tends  to 
become  circumscribed  by  the  formation  of  adhesions  and  the 
exudate  lies  in  a  cavity  resembling  a  pus  cavity.  The  infection  in 
this  region  is  usually  due  to  perforation  of  the  stomach  by  ulcer 
or  by  cancer,  or  it  may  be  due  to  extension  of  infectious  process 
from  the  gall  bladder,  or,  as  in  this  case,  to  perforation  of  the  colon. 
The  disease  is  really  within  the  thoracic  cavity  and  since  gas  from 
the  intestine  is  usually  contained  in  the  space  the  condition  is 
known  as  "  subdiaphragmatic  pyo-pneumo-thorax." 


PLASMODIUM  MALARLE 

Malaria  is  produced  by  a  blood  parasite,  one  of  the  haemosporidia 
which  is  parasitic  in  the  red  blood  corpuscles  of  man.  The  parasite 
undergoes  a  definite  cycle  of  development,  the  sexual  phases  of  which  . 
take  place  within  mosquitoes.  The  disease  is  characterized  by 
periods  of  chill  followed  by  high  fever  which  in  certain  forms  of  the 
disease  occur  with  definite  periodicity,  in  other  forms  are  of  a  more 
irregular  type.  According  to  the  clinical  course  of  the  disease,  it 
has  been  divided  into  different  forms,  each  of  which  is  produced  by  a 
different  species  of  the  parasite. 

The  forms  of  the  disease  are  the  tertian,  in  which  the  paroxysms 
occur  with  one  free  day  in  between,  and  which  is  produced  by  the 
plasmodium  vivax;  the  quartan,  in  which  the  period  of  fever  is 
followed  by  two  days  of  freedom  from  attack  and  which  is  produced 
by  the  plasmodium  malariae;  the  aestivo-autumnal,  in  which  the 
fever  is  of  a  more  irregular  type.  In  certain  cases  the  aestivo- 
autumnal  fever  is  continuous,  closely  resembling  typhoid;  in  other 
cases  slight  attacks  of  fever  occur  daily;  and  in  others  the  fever  takes 
a  pernicious  form,  the  patient  dying  in  coma  during  an  attack.  This 
type  of  malaria  is  produced  by  the  plasmodium  precox  or  falcip- 
arum. 

When  the  blood  is  examined  shortly  after  the  period  of  chill  there 
will  be  found  within  or  on  the  surface  of  certain  of  the  red  blood 
corpuscles  small  ameboid  bodies  about  one-fourth  the  diameter  of 
the  corpuscle.  The  organism  increases  in  size,  successively  attack- 
ing and  destroying  red  blood  corpuscles.  These  lose  their  haemo- 
globin, become  greatly  swollen  and  break  up.  With  the  increase  in 
size  of  the  organism  dark  granules  of  pigment  begin  to  appear,  at 
first  irregularly  distributed  within  the  body,  later  collecting  in  the 
middle.  The  organism  then  divides  into  a  number  of  segments 
which  again  attack  new  corpuscles  and  pass  through  the  same  cycle. 
All  the  organisms  show  the  same  stages  of  development  at  the  same 
period,  and  the  segmentation  corresponds  with  the  period  of  chill. 
In  the  quartan  fever  the  same  stages,  which  in  the  tertian  have  taken 
forty-eight  hours,  take  seventy- two.  In  the  aestivo-autumnal  fever 

317 


3i8  PATHOLOGY 

the  plasmodium  precox  has  a  cycle  of  development  of  forty-eight 
hours,  but  this  probably  is  subject  to  considerable  variation,  while 
the  existence  of  multiple  groups  is  not  infrequent.  This  asexual 
multiplication  of  the  parasite  is  known  as  schizogamy  and  the  young 
parasites  as  merozoites.  The  merozoites,  when  taken  into  the 
alimentary  canal  of  the  mosquito  of  the  genus  anopheles,  undergo 
a  further  development  into  male  and  female  forms  known  respec- 
tively as  micro-  and  macro-gametes,  and  after  fertilization  a  large 
body,  the  ookinet  which  attaches  itself  to  the  intestinal  wall  is 
formed.  Small  sickle-shaped  bodies,  the  sporozoites,  which  pass 
into  the  body  cavity  of  the  mosquito  and  make  their  way  into  the 
salivary  glands  develop  from  the  ookinet.  When  the  insect  bites 
man,  it  injects  a  small  amount  of  saliva,  which  in  the  case  of  in- 
fected mosquitoes,  carries  with  it  the  sporozoites.  These  quickly 
reach  the  blood  and  institute  the  asexual  cycle  of  multiplication. 

The  lesions  in  malaria  are  due  to  the  destruction  of  blood  cor- 
puscles by  means  of  the  parasites  and  to  toxic  substances  which  ap- 
parently are  set  free  when  the  organism  divides,  thus  producing  the 
chill.  There  are  also  lesions  associated  with  the  presence  of  the 
pigment  and  lesions  due  to  the  plugging  up  of  the  capillaries  in 
certain  regions  of  the  body,  particularly  in  the  brain,  by  the  num- 
bers of  organisms  within  them.  During  the  attack  the  spleen  is 
enlarged  and  soft.  When  the  disease  has  persisted,  the  spleen 
remains  enlarged  and  is  dark  or  often  black  from  the  amount  of 
pigment  within  it.  There  is  a  marked  increase  in  the  interstitial 
tissue  of  the  spleen  causing  induration.  The  liver  also  is  somewhat 
swollen  and  within  the  sinusoids  are  great  numbers  of  large  phago- 
cytic  cells  which  contain  pigment.  This  pigment,  which  is  such  a 
characteristic  feature  of  the  disease,  is  autochthonous,  is  produced 
by  the  parasite  and  does  not  contain  iron.  The  aestivo-autumnal 
fever  in  certain  regions  has  a  peculiarly  malignant  type,  death 
taking  place  in  the  period  of  chill.  The  malignant  course  is  to  be 
attributed  either  to  the  presence  of  great  numbers  of  organisms,  or 
to  their  especial  virulence,  or  to  lack  of  resistance  in  the  individual. 
In  death  from  this  condition  the  brain  is  of  a  chocolate  brown  color, 
which  is  due  to  enormous  numbers  of  the  parasites  often  hi  the 
stage  of  segmentation  within  the  capillaries  of  the  gray  matter. 
Large  numbers  of  organisms  may  also  be  found  in  these  conditions 
in  the  spleen  and  in  other  organs. 


PLASMODIUM  MALARLE  319 

A  CASE  OF  PERNICIOUS  MALARIAL  FEVER 

The  patient  was  received  into  the  hospital  in  the  afternoon  of  Sept- 
ember 1 2th,  1884,  in  a  profoundly  comatose  condition,  with  a  tempera- 
ture in  the  axilla  of  101.4°  F.  Sickness  began  two  days  before  with 
complaint  of  loss  of  appetite  and  general  weakness.  He  became  uncon- 
scious in  the  morning  of  the  day  he  was  sent  to  the  hospital.  He  died 
on  September  i3th  at  9  A.M.  without  having  regained  consciousness. 

(Only  the  lesions  associated  with  the  disease  are  noted.) 

The  pia  mater  slightly  thickened  and  cedematous,  easily  stripped  from 
the  surface  of  the  brain.  The  cortex  of  the  brain  throughout  is  of  a  dull 
chocolate  color,  this  color  more  pronounced  in  the  gray  than  in  the  white 
matter,  although  the  white  matter  is  slightly  darker  than  normal,  and 
the  line  of  demarkation  separating  white  from  gray  is  more  pronounced, 
giving  the  gray  matter  the  appearance  of  being  lessened  in  width.  The 
central  ganglia  of  the  brain  are  of  the  same  dark  color  as  the  cortex.  The 
pia  arachnoid  of  the  cord  is  hyperemic,  the  cord  itself  darker,  the  gray 
matter  of  the  same  color  as  the  cerebral  cortex. 

Liver  large,  weight  2126  grams.    Of  a  dark  slaty  color,  very  hyperaemic. 

Spleen  greatly  enlarged,  18  by  10  by  5  cm.,  weight  825  grams;  hy- 
peraemic, of  a  dark,  almost  black,  color. 

On  microscopic  examination  of  the  brain  cortex  with  low  power,  the 
blood  vessels  have  the  appearance  of  being  artificially  injected  with  a 
black  injecting  mass.  With  a  high  power  the  small  granules  of  pigment 
are  found  to  be,  for  the  most  part,  within  small  hyalin  masses  enclosed 
in  red  corpuscles.  Often  the  pigment  granules  are  in  the  centre  of  small 
rosettes  formed  by  segments  radiating  from  a  centre.  The  white  matter 
of  the  brain  also  contains  the  pigmented  bodies,  but  they  are  less  numer- 
ous than  in  the  cortex.  In  the  cord  the  blood  vessels  are  filled  with 
hyalin  pigmented  masses  which  are  more  numerous  in  the  gray  than  in 
the  white  matter.  In  the  spleen  there  is  a  large  amount  of  pigment,  in 
part  free,  in  part  contained  in  large  endothelial  cells,  and  in  part  contained 
in  minute  masses  within  the  parasites.  In  the  liver  the  sinusoids  contain 
great  numbers  of  large  endothelial  phagocytic  cells  filled  with  pigment 
granules  of  irregular  size. 

REMARKS.  The  condition  is  sufficiently  explained  by  the  pre- 
ceding text. 


SMALL  POX 

This  is  an  acute  infectious  disease  characterized  by  a  pustular 
eruption  on  the  skin.  The  skin  lesions  begin  as  vesicles  which  later 
are  converted  into  pustules.  The  factors  concerned  in  the  produc- 
tion of  the  vesicles  are  degeneration  of  the  epithelial  cells  associated 
with  or  followed  by  an  exudation  into  the  epidermis.  The  degene- 
rated cells  form  a  reticulum  within  the  meshes  of  which  the  exuda- 
tion accumulates.  Section  of  the  vesicle  shows  a  fan-shaped  reticular 
structure  within  the  epidermis  and  a  varying  number  of  leucocytes 
in  the  spaces.  In  the  corium  the  blood  vessels  are  congested  and 
there  is  a  slight  exudation  about  them.  As  the  exudation  increases 
the  tension  becomes  great,  and  strands  of  the  reticulum  rupture  and 
large  spaces  separated  by  shreds  of  epithelium  are  formed.  The 
vesicle  becomes  converted  into  a  pustule  by  the  accumulation  of 
leucocytes  in  the  exudation.  In  slight  lesions  the  malpighian  layer 
of  epidermis  may  be  intact,  but  in  the  more  extensive  lesions  not 
only  is  the  entire  epidermis  involved,  but  there  also  is  necrosis  of 
the  papillae.  When  the  papillae  of  the  corium  are  destroyed  a 
smooth  depressed  cicatrix  remains  after  healing.  In  most  cases  the 
pustules  are  depressed,  in  the  centre,  umbilicated,  due  to  the  pres- 
ence in  the  centre  of  more  resistant  epithelial  structures  such  as 
ducts  of  sweat  glands  or  hair  follicles.  The  pustules  vary  in  size 
from  2  to  8  mm.  The  severity  of  the  disease  usually  is  in  direct 
proportion  to  the  extent  of  the  eruption.  The  pustules  may  be 
single  and  few  in  number,  discrete  smallpox,  or  so  numerous  that 
adjoining  vesicles  coalesce,  confluent  smallpox.  The  eruption 
appears  first  and  the  pustules  are  more  numerous  on  the  face. 
They  are  more  numerous  on  the  extremities  than  on  the  trunk. 
In  certain  severe  forms  of  the  disease  the  exudation  may  have  a 
haemorrhagic  character  variola  pustulosa  hamorrhagica.  A  special 
form  of  the  disease,  purpura  variolosa  (black  smallpox),  is  char- 
acterized by  intense  congestion  and  haemorrhage  of  the  skin  and  a 
slight  development  of  pustules.  The  erythyma  develops  quickly 
after  the  onset  of  the  disease  and  death  takes  place  before  the  pus- 
tules develop. 

320 


SMALL  POX  321 

The  cause  of  smallpox  remains  obscure.  In  the  lesions  of  the 
skin,  bodies  of  peculiar  character  are  found  in  the  epithelial  cells 
in  a  space  adjoining  the  nucleus  (cytoryctes  variolae).  They  are 
invariably  present  and  reach  the  acme  of  their  development  before 
the  pustular  stage;  with  the  development  of  the  pustule,  peculiar 
vacuolated  bodies  appear  in  the  nuclei.  In  vaccinia,  which  must 
be  regarded  as  a  form  of  smallpox,  the  virus  of  which  is  modified 
by  passing  through  the  cow,  inclusions  in  the  epithelial  cells  similar 
to  those  found  in  the  vesicular  stage  of  smallpox  are  invariably 
present.  The  inclusions  within  the  nuclei  of  the  epithelial  cells 
are  not  found  in  vaccinia.  These  inclusions  have  been  regarded  as 
living  organisms  related  to  the  protozoa,  the  reason  for  this  con- 
clusion being  based  on  their  invariably  presence  in  the  disease  in 
association  with  the  lesions  and  under  no  other  conditions,  the 
evidence  of  growth  and  development  which  they  show  and  the  dis- 
similarity with  other  products  formed  in  cells  as  the  result  of 
degeneration.  The  positive  proof  for  this  conception  of  their 
nature,  which  could  be  given  by  isolation  and  culture,  is  absent. 

Lesions  in  their  main  characteristics  similar  to  those  of  the  skin 
are  found  in  the  mucous  membrane  of  the  mouth  and  pharynx. 
Typical  vesicles  and  pustules  do  not  form,  owing  to  the  absence  of 
the  impenetrable  horny  layer.  In  addition  to  these  lesions  of  the 
skin  and  mucous  membranes,  lesions  equally  characteristic,  but  not 
so  constant,  occur  in  the  testicles  and  in  the  bone  marrow.  In  the 
testicles  the  lesions  take  the  form  of  small  foci  of  necrosis  of  the 
tubules,  with  haemorrhage  and  fibrinous  exudation  in  the  interstitial 
tissue  and  with  infiltration  of  cells  of  the  lymphoid  type.  They 
appear  as  small  red  foci  rarely  more  than  2  mm.  in  diameter.  The 
lesions  in  the  marrow  consist  in  degeneration,  focal  in  character, 
apparently  not  anaemic,  but  due  to  toxic  action,  leading  to  necrosis 
often  associated  with  haemorrhage,  and  accompanied  by  focal 
formation  of  phagocytic  cells. 

Diffuse  toxic  degeneration  is  present  hi  the  liver,  the  kidneys, 
the  adrenal  glands  and  the  testicles;  in  the  liver  cloudy  swelling 
is  more  marked  than  it  is  in  any  other  infectious  disease  and  gives 
rise  to  a  considerable  increase  in  the  weight  of  the  organ. 

Secondary  bacterial  infections,  particularly  with  streptococci, 
play  an  important  r61e  in  the  pathology  of  the  disease  and  in  most 
cases  death  is  to  be  attributed  to  such  secondary  infection.  The 


322  PATHOLOGY 

infection  with  bacteria  often  extends  from  the  specific  lesions  of 
the  mucous  membrane  of  the  mouth  or  pharynx  into  the  adjoining 
tissue,  producing  extensive  necrosis  and  oedema.  Bacteria  in  large 
masses  may  be  found  in  the  tissue  growing  as  in  culture  and  without 
any  leucocytic  reaction  about  them.  Broncho-pneumonia  also  is 
common  and  may  be  extensive. 

Smallpox  is  transmitted  through  the  placenta  and  children  are 
born  with  characteristic  skin  lesions,  and  in  some  cases  with  the 
cicatrices  which  follow  them,  having  passed  through  the  disease  in 
utero. 

A  CASE  OF  SMALLPOX 

Anatomical  Diagnoses.  Variola  confluens,  crusting  on  face,  pustu- 
lar and  vesicular  elsewhere;  (Edema  of  lungs;  Focal  necrosis  of 
the  testes;  Focal  lesions  of  the  pharynx,  trachea,  oesophagus,  and 
urethra;  Acute  laryngitis,  tracheitis  and  bronchitis;  Plegmonous 
inflammation  of  neck  and  anterior  mediastinum. 

Clinical  Diagnosis.    Variola  vera  (twelve  days'  duration.) 

Body  of  a  well-developed  and  well-nourished  man,  thirty-six  years  of 
age.  Rigor  mortis  present  and  fully  developed. 

The  face  and  neck  present  a  confluent  mass  of  soft,  moist,  brown 
crusts.  The  nostrils  are  almost  occluded  by  crusts.  Left  eye  is  absent 
(old  injury).  Right  eye  and  conjunctiva  normal,  pupil  of  normal  size. 
Over  the  trunk  there  are  numerous  late  vesicles  and  early  pustules. 
The  lesions  are  four  to  eight  millimeters  in  diameter,  are  of  the  color  of 
the  skin,  show  a  marked  umbilication,  and  sometimes  have  a  slightly 
oval  outline.  These  lesions  are  not  very  closely  set  (about  one  to  a 
centimeter  square.) 

On  the  arms  and  legs  are  many  lesions  like  those  on  the  body,  but  they 
are  more  closely  set  and  somewhat  larger,  particularly  on  the  dorsum  of 
the  hands.  On  the  penis  and  scrotum  are  a  considerable  number  of 
similar  lesions. 

On  the  thighs  are  closely  set,  umbilicated  vesicles,  like  those  described 
on  the  body.  The  lesions  here  are  about  two  or  three  to  the  square 
centimeter.  On  the  legs  and  dorsa  of  the  feet  the  lesions  are  fewer  in 
number  and  are  less  umbilicated.  There  is  no  clustering  of  the  lesions 
and  in  the  groins  and  flanks  they  are  comparatively  few  in  number. 
There  is  a  purulent  balanitis. 

On  section,  subcutaneous  fat  3  cm.  thick.  Muscles  deep  red.  Mesen- 
teric  lymph  nodes  and  appendix  normal. 


SMALL  POX  323 

Thorax.  Pleural  cavities;  surf  aces  normal.  Pericardial  cavity  normal, 
contains  a  few  c.c.  of  clear,  straw-colored  fluid. 

Heart.  Weight  260  grams.  Myocardium  pale  brown  red.  Right 
ventricle  flabby  and  filled  with  yellow  clot.  Left  ventricle  firmly  con- 
tracted. Valves  and  cavities  normal. 

Lungs.  On  the  outer  aspect  of  the  left  lower  lobe  is  an  area  of  thick- 
ened pleura  1.5  cm.  across,  which  is  of  a  pearly- white  color  and  with  a 
serrated  border.  Lungs  alike.  Crepitant  throughout.  On  section,  cut 
surface  mottled  light  and  deep  pink  with  distinct  carbon  markings. 
Surface,  on  gentle  pressure,  yields  considerable  clear  fluid  containing 
innumerable  bubbles  of  air.  Bronchial  mucosa  normal.  Bronchi  con- 
tain stringy  mucus. 

Abdomen.    Peritoneal  cavity  normal. 

Spleen.  Weight  200  grams.  Color,  deep  purple.  On  section  cut 
surface  deep  red,  malpighian  bodies  visible  as  gray  points;  trabeculae 
normal.  Consistency  is  firm,  and  little  substance  adheres  to  knife  on 
gentle  scraping. 

Pancreas  normal. 

Stomach.  Some  diffuse  ecchymoses  along  lesser  curvature.  Mucosa 
normal. 

Intestines;  normal. 

Liver.  Weight  2650  grams.  Surface  smooth  and  of  a  yellow-brown 
color.  On  section,  markings  indistinct.  Consistency  normal.  On  the 
surface  are  irregular  yellow  areas  which  are  contoured  in  such  wise  as  to 
suggest  aggregations  of  fatty  lobules.  On  section  similar  markings  are 
found.  Gall  bladder  normal. 

Kidneys.  Weight  350  grams.  Surface  yellow  brown.  Capsule  strips 
readily,  leaving  a  smooth  surface.  On  section  markings  are  indistinct. 
Glomeruli  visible  as  gray  points.  Cortex  of  normal  thickness  and  of  a 
yellow-brown  color.  Pyramids  reddish  brown. 

Adrenals  normal.    Bladder  normal. 

Genitals;  urethra.  About  midway  hi  the  penile  portion  is  an  elevated 
area  2  mm.  across,  with  an  irregular,  oval  outline  and  with  a  central 
depression.  Elsewhere  urethra  is  normal.  Seminal  vesicles  and  epi- 
didymis  normal.  Prostate  normal.  Testes;  tunica  vaginalis  normal, 
slightly  nodular  to  the  feel.  On  section  the  markings  are  distinct,  but 
scattered  over  the  cut  surface  are  nodular  elevations  i  to  3  mm.  across, 
which  are  redder  than  the  surrounding  tissue.  These  areas  are  not 
sharply  circumscribed,  and  in  them  the  tubular  markings  are  visible. 

Lymph  nodes  of  the  groin  are  enlarged,  red  and  somewhat  hard. 
(Largest,  2  cm.  across.) 

Aorta  normal. 


324  PATHOLOGY 

Organs  of  neck.  Soft  palate;  uvula  and  pharynx  show  low,  gray 
nodular  elevations,  some  of  which  present  a  central  superficial  loss  of 
substance. 

Epiglottis  thickened  and  similarly  beset  with  nodules. 

Larynx  contains  much  gray  mucus  and  its  mucous  membrane  is 
reddened.  In  the  trachea  are  numerous  elevations  from  i  to  3  mm.  in 
diameter,  surrounded  by  a  red  ring.  These  elevations  are  conical  and 
are  occasionally  eroded.  About  thirty  such  lesions  of  various  sizes  are 
present.  (Esophagus,  upon  its  mucous  membrane,  presents  many  pale 
gray,  oval  or  circular  elevations,  from  i  to  3  mm.  in  diameter.  The 
largest  of  these  is  a  low  cone,  of  a  translucent  gray  color,  surrounded  by 
a  narrow  elevated  rim  like  the  hull  of  an  acorn;  this  surrounding  rim 
is  red. 

The  deep  tissues  of  the  neck  on  the  right  side  are  infiltrated  with  a 
grayish  material,  and  on  section  a  considerable  amount  of  turbid,  slightly 
blood-stained  fluid  exudes.  The  jugular  vein  is  filled  with  a  yellow  clot 
and  its  wall  appears  normal.  The  muscles  close  about  the  larynx  are  in 
part  friable  and  of  an  opaque,  yellow-brown  color.  The  fibrillary  mark- 
ings are  indistinct.  The  tissue  of  the  anterior  mediastinum  is  cedem- 
atous,  and  on  section  a  cloudy,  faintly  blood-stained  fluid  exudes.  This 
condition  is  most  marked  over  the  precordium  and  about  the  remnant 
of  the  thymus.  Left  side  of  neck  normal. 

Bone  marrow,  in  general,  yellow  with  many  areas  of  deep  red  color. 

REMARKS.  The  case  is  one  of  typical  smallpox  with  death  on  the 
twelfth  day  of  the  disease.  The  character  and  distribution  of  the 
eruption  on  the  skin  is  the  usual.  The  pustule  in  the  urethra  is  an 
unusual  localization.  The  extensive  infection  of  the  neck  which 
has  extended  into  the  mediastinum  is  due  to  streptococci  which 
probably  have  entered  the  tissue  from  the  tonsil  or  pharynx.  The 
character  of  the  lesions  in  the  mucous  membrane  with  the  generally 
eroded  surface  is  interesting  in  contrast  to  the  pustules  in  the  skin. 


MEASLES 

This  is  an  acute  infectious  disease  characterized  by  a  maculo- 
papular  eruption  of  the  skin  and  mucous  membranes. 

An  incubation  period,  usually  of  fourteen  days,  is  followed  by 
fever,  coryza,  bronchitis  and  the  appearance  on  the  buccal  mucosa 
of  white  or  bluish-white  specks  surrounded  by  a  small  red  areola. 
(Koplik's  spots.)  The  cutaneous  eruption  appears  first  behind  the 
ears,  then  extends  to  neck,  forehead  and  face,  thence  to  the  trunk 
and  extremities.  The  eruption  consists  of  small  macules  of  light 
red  color,  vaguely  denned  and  often  confluent,  whose  elevation  is 
so  slight  as  to  be  more  readily  detected  by  touch  than  by  the  eye. 

This  disease  is  made  a  serious  one  by  the  frequent  development 
of  broncho-pneumonia.  Otitis  media  frequently  is  a  concomitant 
and  sequel;  acute  nephropathy  is  not  infrequent. 


325 


SCARLET  FEVER 

An  acute  infectious  disease  characterized  by  diffuse  erythematous 
eruption.  The  gross  pathological  lesions  are  slight  and  the  eryth- 
ema usually  does  not  show  after  death.  The  only  constant  gross 
change  is  hyperplasia  of  the  lymphoid  tissue  generally.  The  blood 
vessels  of  the  corium  are  dilated  more  especially  near  the  epidermis 
and  in  the  papillae.  The  superficial  lymphatics  and  lymph  spaces 
likewise  show  dilatation  in  the  same  situation.  With  these  changes 
there  is  a  slight  exudation.  Leucocytes,  in  small  numbers,  migrate 
from  the  blood  vessels  and  are  found  hi  the  corium  and  invading 
the  epidermis.  In  the  tongue  there  are  pathological  conditions 
similar  to  those  in  the  skin,  but  they  begin  earlier  and  are  more 
marked  and  the  same  is  true  of  the  mucous  membrane  of  the  pharynx 
and  tonsils.  Bodies  which  have  been  interpreted  by  some  as 
products  of  cell  degeneration  and  by  others  as  protozoa  occur  in  the 
epidermis  in  association  with  the  lesions  (cyclasterion  scarlatinalis). 
These  bodies  are  found  lying  in  vacuoles  in  the  epithelial  cells  of 
the  epidermis,  to  a  less  extent  between  these  cells,  and  free  in  the 
superficial  lymph  vessels  and  spaces  of  the  corium.  Associated  with 
these  specific  changes  frequently  are  found  broncho-pneumonia  and 
otitis  media  which  are  due  not  to  the  specific  cause  of  scarlet  fever 
but  to  secondary  infections  usually  with  the  streptococcus.  The 
period  of  incubation  usually  is  four  or  five  days. 

A  CASE  OF  SCARLET  FEVER 

Anatomical  Diagnoses.  Focal  hypersemia  of  the  skin  with  slight 
desquamation  (scarlet  fever);  Thrombi  in  heart;  Acute  endo- 
carditis of  mitral  and  aortic  valves;  Acute  pericarditis;  Acute 
peritonitis;  Acute  bronchitis  and  broncho-pneumonia;  Acute 
interstitial  nonsuppurative  nephropathy;  Fatty  degeneration  of 
the  heart;  Focal  necrosis  of  the  liver;  Acute  otitis  media; 
Streptococcus  and  pneumococcus  infection. 

Female,  white,  age  five  years.  There  are  irregularly  placed  areas  of 
hyperaemia  of  the  skin  most  marked  over  the  neck,  posterior  part  of  the 
body  and  legs,  and  over  the  anterior  surface  of  chest  and  arms.  In  these 

326 


SCARLET  FEVER  327 

areas  there  are  small  elevated  points  with  slight  exfoliation  of  the  epi- 
dermis. 

The  abdomen  is  slightly  distended  and  the  cavity  contains  a  small 
amount  of  clear  fluid.  Over  the  surface  of  the  liver  there  is  a  thin  layer 
of  fibrin,  and  over  the  peritoneal  surface  elsewhere  a  few  areas  covered 
with  a  slight  fibrinous  exudation. 

The  pleural  surfaces  on  the  right  side  are  adherent  by  fibrous  tissue; 
on  the  left  free.  The  pericardial  cavity  contains  a  small  amount  of 
cloudy  fluid.  Both  the  visceral  and  parietal  surfaces  are  covered  with 
a  thin  layer  of  fibrin. 

Heart,  weight,  100  grams.  In  the  right  auricle  near  the  auricular 
appendix  is  a  small  white  adherent  thrombus,  i  cm.  in  diameter,  and  in 
the  appendix  a  number  of  small  thrombi.  Along  the  line  of  apposition 
of  the  mitral  valve  there  are  numerous  small  gray  elevations,  the  largest 
i  mm.  in  diameter.  On  one  of  the  cusps  of  the  aortic  valve  there  is  a 
small  group  of  similar  granulations.  The  myocardium  is  pale,  and  in 
one  of  the  papillary  muscles  there  are  numerous  yellow-white  foci. 

The  lungs  are  distended.  The  pleural  surface  hyperaemic  with 
scattered  foci  of  more  marked  hyperaemia  and  which  are  solid  to  the 
touch.  On  section  the  lungs  are  congested  and  cedematous,  and  through- 
out there  are  small  pale  red  areas  of  solidification  from  0.5  to  i  cm.  in 
diameter  and  from  which  a  purulent  fluid  can  be  expressed.  The  mucous 
membrane  of  the  bronchi  is  reddened  and  a  purulent  exudation  can  be 
expressed  from  thin  sections  in  the  lung. 

Spleen,  weight,  105  grams,  firm,  dark  red,  follicles  prominent. 

Kidneys,  weight,  195  grams.  The-  capsule  slightly  adherent,  the 
surface  hyperaemic  and  shows  small  punctate  haemorrhages.  On  section 
contrast  between  pyramids  and  cortex  diminished,  the  pyramids  paler 
than  normal,  the  cortex  swollen,  the  normal  markings  obliterated. 
Throughout  the  cortex  there  are  numerous  small  points  and  streaks  of 
gray.  At  the  base  of  the  pyramids  are  numerous  small,  round  or  irregu- 
lar gray  areas,  most  of  them  from  i  to  2  mm.  in  diameter,  some  up  to 
4  mm.  Some  of  these  areas  extend  as  lines  to  the  cortex  and  occasionally 
they  are  present  elsewhere  in  the  pyramid  than  at  the  base.  They  often 
are  surrounded  by  an  irregular  red  zone  of  vascular  injection. 

Liver,  weight,  675  grams.  Of  a  red-gray  color,  and  both  the  surface 
and  section  show  numerous  minute  opaque,  yellow-white  points. 

The  mucous  membrane  of  pharynx  congested.  The  tonsils  large,  the 
crypts  filled  with  tough  white  masses. 

All  the  lymph  nodes  of  the  body  are  enlarged  and  hyperaemic. 

The  bone  marrow  of  femur  abundant  and  pale  red  in  color. 

The  left  middle  ear  contains  muco-purulent  material. 


328  PATHOLOGY 

The  gastrointestinal  canal  normal  save  for  slight  swelling  of  the 
lymph  follicles.  Cultures  from  the  peritoneum,  the  pericardial  cavity 
and  the  vegetations  on  the  mitral  valve  gave  pure  cultures  of  strepto- 
cocci. From  the  lungs  streptococci  and  pneumococci  were  obtained. 

Microscopical  examination  of  the  liver  showed  scattered  circum- 
scribed foci  of  necrosis,  not  central  and  without  any  relation  of  situation 
to  the  lobule.  Large  numbers  of  polynuclear  leucocytes  were  found  in 
the  sinusoids  and  within  the  cell  trabeculae. 

The  kidneys  showed  very  marked  cloudy  swelling  and  fatty  degenera- 
tion of  the  epithelium  of  convoluted  tubules.  In  streaks  and  in  foci  there 
was  infiltration  of  the  intertubular  tissue  with  large  cells  of  the  lymphoid 
type.  In  the  foci  of  such  infiltration  the  cell  degeneration  was  not  more 
marked  than  elsewhere. 

The  myocardium  in  addition  to  fatty  degeneration  showed  foci  of 
infiltration  with  cells  of  the  same  type  as  those  in  the  kidney. 

REMARKS.  A  death  from  scarlet  fever  with  an  unusual  extent 
of  streptococcus  infection.  The  lesions  most  immediately  associated 
with  the  scarlet  fever  are  the  bronchitis  and  broncho-pneumonia 
and  the  otitis  media,  which  are  due  to  secondary  infection.  The 
acute  interstitial  nephropathy  (the  pathology  of  which  will  be 
further  discussed  under  "Kidney,"  page  350)  is  also  a  condition 
not  unusual  in  the  exanthemata.  There  was  also  streptococcus 
infection  of  the  blood  to  which  the  acute  endocarditis,  the  peri- 
carditis and  the  peritonitis  must  be  attributed.  Infection  of  the 
peritoneum  originating  in  other  ways  than  by  extension  from  the 
intestine  or  from  some  other  focus  is  rare,  but  takes  place. 


ACUTE  ANTERIOR  POLIOMYELITIS 

An  acute  infectious  disease  with  characteristic  lesions  in  the 
central  nervous  system.  The  cause  of  the  disease  and  the  mode  of 
entry  of  the  organism  are  unknown.  Only  man  and  the  monkey 
are  susceptible.  The  virus  is  filterable  and  has  been  shown  by  the 
inoculation  of  animals  to  be  present  in  the  central  nervous  system 
and  in  the  mucous  membrane  of  the  pharynx.  The  lesions  are 
inflammation  of  the  pia-arachnoid  with  serous  or  sero-haemor- 
rhagic  exudation,  degeneration  of  the  gray  matter  of  the  cord  and 
infiltration  of  the  tissue  with  endothelial  cells.  The  vessels  of  the 
pia  and  brain  are  congested,  the  perivascular  spaces  in  the  brain 
dilated;  there  often  are  haemorrhages  about  the  vessels.  The 
degeneration  and  cellular  infiltration  usually  is  most  intense  in  the 
cervical  cord,  usually  involves  the  entire  length  of  the  cord  and  may 
affect  the  medulla  and  the  pons.  In  these  regions  there  is  intense 
cellular  infiltration  around  the  vessels  and  in  the  tissue  of  the  gray 
matter.  The  ganglion  cells  are  degenerated  and  often  completely 
destroyed.  Polynuclear  leucocytes  take  no  part  in  the  process. 
The  endothelial  cells  come  into  the  region  partly  by  migration, 
partly  from  proliferation  of  the  endothelial  cells  of  the  tissue. 
Nuclear  figures  are  found  in  them.  The  cells  of  the  neuroglia  are 
swollen,  increased  in  number,  the  fibrils  larger  and  more  conspicu- 
ous. Conditions  in  the  main  similar  to  those  in  the  cord  are  found 
in  the  spinal  ganglia.  There  usually  is  a  general  hyperplasia  of  the 
lymphoid  system  and  acute  congestion  of  the  spleen.  The  disease 
is  more  common  in  children  than  in  adults. 

A  CASE  OF  POLIOMYELITIS 

Anatomical  Diagnoses.  Poliomyelitis;  Hyperplasia  of  lymphoid 
tissue;  Congestion  and  haemorrhage  of  intestine;  Chronic  hepat- 
itis; Chronic  adhesive  pleuritis;  Congestion  of  spleen. 

Male,  white,  age  five  years.     Body  well  developed  and  well  nourished, 
surface  normal. 

Peritoneal  cavity  normal. 

Both  pleural  cavities,  but  particularly  the  left  nearly  obliterated  by 
tough,  fibrous  adhesions.     Cavities  contain  no  fluid. 

329 


330  PATHOLOGY 

Pericardial  cavity  normal. 

Heart  weighs  90  grams.    Normal. 

Lungs.    Both  crepitant  throughout. 

Liver.  Weight  600  grams.  On  the  surface  there  are  small  pale 
depressions,  most  marked  on  anterior  surface  near  region  of  the  gall 
bladder.  The  edges  of  liver  are  irregular.  The  capsule  is  thickened. 

Gall  bladder  and  ducts  are  normal. 

Pancreas  normal. 

Spleen,  weight,  90  grams.    Capsule  tense,  organ  of  dark  red  color. 

Kidneys.  Combined  weight  no  grams.  Pyramids  somewhat  con- 
gested. 

Gastro-intestinal  track.  Stomach  normal.  In  the  lower  portion  of 
the  ileum  the  Peyer's  patches  are  enlarged,  elevated,  the  vessels  injected 
and  hi  some  are  small  areas  of  haemorrhage.  The  solitary  follicles  also 
are  enlarged  and  a  few  foci  of  haemorrhage  are  seen. 

Lymph  nodes.  The  mesenteric  lymph  nodes,  especially  those  of  the 
ileo-caecal  region,  are  enlarged.  The  largest  of  these  is  2  cm.  in  diameter. 

Organs  of  neck  not  examined. 

Brain.  Calvarium  and  dura  normal.  The  vessels  of  pia  mater  deeply 
injected.  In  places  there  are  small  haemorrhages  from  0.2  to  i  cm.  in 
diameter.  In  places  these  are  so  numerous  as  to  become  confluent. 
The  haemorrhages  are  most  marked  over  the  temporal  lobe  posteriorly. 
The  vessels  at  base  of  brain  are  normal.  The  pia  strips  easily.  The 
brain  is  moist,  the  small  vessels  are  prominent.  The  ventricles  contain 
clear  fluid,  the  ependyma  is  smooth  and  glistening.  In  the  region  of 
the  olivary  body  on  the  right  side  there  is  a  small,  pale  yellow  area  about 
i  mm.  in  diameter. 

Spinal  cord  shows  lesions  of  varying  extent  which  are  most  marked  in 
the  cervical  region.  Here  the  anterior  horns  have  in  part  lost  their  normal 
outline,  in  part  haemorrhages  are  seen  in  them.  The  haemorrhages  are 
usually  small  and  punctate,  and  are  not  symmetrical  in  distribution. 
The  gray  matter  appears  swollen  and  irregular,  the  contrast  with  the 
white  is  not  so  sharp;  apart  from  the  haemorrhages  there  is  a  diffused 
redness.  This  character  of  the  gray  matter  extends  through  all  the  cord. 

REMARKS.  The  lesions  of  the  central  nervous  system  in  this 
case  are  typical  of  the  disease.  Associated  with  the  disease  are 
the  hyperplasia  of  the  lymphoid  tissue  with  haemorrhage  and  the 
acute  congestion  of  the  spleen.  The  chronic  hepatitis  is  an  unusual 
condition  in  a  child  of  this  age  and  very  possibly  associated  with 
some  antecedent  infection.  Such  extensive  pleuritic  adhesions 
also  are  unusual  in  children. 


PARASITIC  WORMS* 

Cestodes  or  tapeworms  are  not  uncommon  parasites  in  man;  the 
adult  worm  inhabits  the  alimentary  canal  and  the  larval  forms 
occasionally  invade  the  tissues.  These  worms  are  jointed,  they 
consist  of  a  head  or  scolex  which  adheres  to  the  intestinal  mucous 
membrane  and  joints  or  proglottides,  in  which  there  is  hermophro- 
ditic  sexual  differentiation.  By  the  great  number  of  proglottides 
which  may  form  the  worm  may  attain  a  length  of  ten  meters  or 
more.  The  sexual  organs,  both  male  and  female,  are  found  in  the 
segment  and  numerous  eggs  are  discharged  from  the  single  opening. 
The  eggs,  which  are  provided  with  a  chitinous  membrane,  develop 
into  an  embryo  or  onchosphere  which,  still  enclosed  in  the  membrane, 
is  taken  into  the  alimentary  canal  of  a  suitable  host.  This  pene- 
trates the  intestinal  mucous  membrane  and  enters  the  lymph  or 
blood  stream  and  is  deposited  in  the  tissues.  There  it  develops 
into  a  vesicle,  cystocercus,  from  some  part  of  which  one  or  numerous 
scolices  are  developed.  These,  when  taken  into  the  alimentary 
canal  of  the  primary  host,  develop  into  the  adult  worms. 

Of  these  worms,  three  are  important,  tania  saginata  or  beef  tape- 
worm; tania  solium  or  pork  tapeworm;  and  dibothriocephalus 
latus  or  fish  tapeworm.  The  worms  infest  man  as  their  primary 
host  and  develop  in  his  intestinal  canal,  the  scolex  of  the  first  two 
being  attached  by  means  of  both  booklets  and  suckers  and  that  of 
the  fish  worm  by  means  of  suckers  only.  The  proglottides  of  the 
first  two  are  longer  than  they  are  broad,  when  fully  developed, 
whereas  those  of  the  fish  worm  are  broader  than  they  are  long. 
Numerous  other  differences  can  easily  be  made  out  by  minute 
examination.  The  fish  worm  infestation  is  most  serious  because 

*  It  is  not  possible  to  discuss  fully  these  parasites  in  the  limitation  of  space  which 
this  treatise  demands,  and  the  same  is  true  of  the  animal  parasites  generally.  Only 
those  animal  parasites  have  been  considered  which  have  appeared  to  the  author  as 
most  important  both  in  their  pathogenic  properties  and  as  types.  Excellent  descrip- 
tions can  be  found  in  all  text  books  of  medicine.  Only  the  most  common  of  these 
parasites  which  actually  invade  the  tissues  either  in  the  adult  or  larval  form  will  be 
discussed  here. 

331 


332  PATHOLOGY 

the  subject  may  become  the  victim  of  a  serious  anaemia,  closely 
resembling  pernicious  anaemia  and  probably  caused  by  the  absorp- 
tion of  a  haemolytic  lipoid  found  in  the  segments. 

When  the  onchospheres  of  taenia  solium  enter  the  stomach  of  man, 
cystiocirci  cellulosae  are  found  in  some  organ  generally  remote  from 
the  alimentary  canal.  In  its  typical  form  this  is  an  elliptical  vesicle 
from  i  to  2  cm.  in  the  long  and  from  0.5  to  i  cm.  in  the  short 
diameter.  In  the  interior  a  white  point,  the  invaginated  scolex, 
can  be  recognized.  The  membrane  of  the  vesicle  is  characteristic 
in  its  homogeneous  refractive  structure  and  its  smooth,  linear,  in- 
ternal contour.  Such  cystocerci  are  especially  common  in  the  brain, 
but  may  occur  in  any  of  the  organs.  They  may  occur  in  great 
numbers  in  the  muscles  or  subcutaneous  tissue.  They  produce  de- 
generation and  various  types  of  reaction  in  the  tissue  about  them. 

A  form  of  cystiocercus  known  as  the  echinococcus  cyst  arises  in 
man  as  the  secondary  host  from  swallowing  the  onchospheres  of 
the  t&nia  echinococcus,  a  very  short  tapeworm  found  in  the  dog. 
These  cysts  may  be  very  large  and  innumerable  scolices  may  be 
formed  in  them.  The  wall  consists  of  two  layers,  the  outer  com- 
posed of  numerous  transparent  lamellae,  and  an  inner  so-called 
parenchymatous  layer  which  is  granular  and  contains  glycogen. 
From  this  parenchymatous  layer  small  cysts  or  brood  capsules 
develop  each  of  which  may  contain  numbers  of  scolices.  The  fluid 
of  the  cyst  is  colorless  or  slightly  yellow  and  contains  no  albumen. 
The  cysts  grow  slowly  in  size  and  may  attain  large  dimensions. 
They  are  most  common  in  the  liver,  but  may  be  found  in  other 
situations. 

The  Nematodes  or  round  worms  are  very  common.  Some  are  only 
rarely  harmful,  others  are  of  considerable  pathological  import- 
ance. The  size  varies  greatly.  The  sexes  are  separate,  the  male 
usually  is  smaller  than  the  female  and  often  has  the  posterior  ex- 
tremity rolled  up.  They  contain  a  digestive  canal  extending  from 
the  mouth  to  the  anus.  Either  ova  or  embryos  are  discharged,  the 
latter  being  sometimes  larvae  which  undergo  a  further  metamorpho- 
sis before  becoming  worms.  Infestation  may  be  direct  or  by  the 
intermediary  of  another  host. 

The  trichocephalus  trichiurus  (dispar)  is  a  widely  distributed  para- 
site. The  anterior  end  is  hair-like,  the  posterior  end  thickened,  and 
in  the  male  rolled  into  a  spiral.  The  male  is  from  40  to  45  mm.  in 


PARASITIC  WORMS  333 

length,  the  female  from  45  to  50  mm.  They  are  found  in  the  caecum, 
vermiform  appendix  and  colon  and  the  anterior  whip-like  end  is 
embedded  in  the  mucous  membrane.  It  is  evident  from  the  iron- 
containing  pigment  of  the  alimentary  canal  of  the  parasite  that  it 
ingests  blood.  When  hi  large  numbers  considerable  degrees  of 
anaemia  accompany  their  presence.  The  frequent  presence  of  these 
parasites  in  the  vermiform  appendix  suggests  that  they  may  play  a 
role  in  the  production  of  appendicitis,  by  favoring  a  more  important 
bacterial  invasion  through  the  slight  traumas  which  they  produce. 

The  trichinella  spiralis,  in  its  adult  condition,  inhabits  the  small 
intestine.  The  female  is  from  3  to  4  mm.  long  and  0.06  mm.  in 
diameter,  the  male  is  much  smaller,  1.5  mm.  long  and  0.04  mm. 
thick.  The  life  of  the  parasite  is  short,  embryos  being  produced  in 
from  five  to  seven  weeks,  after  which  the  adult  worm  dies.  Infec- 
tion takes  place  by  eating  meat  which  contains  the  embryos.  The 
parasites  are  freed  from  the  capsules  which  surround  them  and 
quickly  develop  into  sexual  ripeness,  fecundation  taking  place  two 
to  four  days  after  infection.  The  male  then  dies  and  the  female 
at  once  wholly  or  partly  penetrates  the  mucous  membrane.  Each 
female  produces  as  many  as  1500  embryos  which  enter  into  the  lym- 
phatics. A  part  of  them  are  retained  in  the  mesenteric  lymph  nodes, 
but  the  mass,  passed  by  means  of  the  thoracic  duct  into  the  blood, 
is  carried  into  the  striated  muscles  of  the  body  with  the  exception 
of  the  heart.  They  are  first  found  within  the  muscle  fibres  in  an 
elongated  shape  and  separated  from  the  contractile  substance  by  a 
clear  border.  In  the  further  growth  they  become  rolled  into  a  spiral 
within  the  fibre.  A  hyalin  capsule  in  which  lime  salts  are  de- 
posited forms  around  the  parasite.  The  severity  of  the  disease 
depends  upon  the  number  of  infecting  parasites. 

Ankylostoma  duodenale  is  the  name  of  the  European  and  uncina- 
ria  americana  the  name  of  the  American  species  of  a  nematode 
which  inhabits  the  alimentary  canal  and  produces  serious  anaemia 
by  blood  destruction.  In  the  fresh  condition  the  worm  is  pale  red 
in  color,  the  male  i  cm.  long  and  0.5  mm.  thick  and  has  on  the 
posterior  end  a  characteristic  bursa  by  which  it  fastens  to  the  female 
in  copulation;  the  female  is  slightly  longer  and  pointed  at  the 
posterior  end.  The  eggs,  when  passed,  are  generally  in  the  stage  of 
segmentation.  The  head  is  provided  with  sharp  teeth  or  plates 
by  which  the  worm  bites  into  the  mucous  membrane  and  sucks  the 


334  PATHOLOGY 

blood.  The  anaemia  is  due  to  the  loss  of  blood  which  is  devoured 
by  the  parasite,  to  the  slight  haemorrhages  which  take  place  from 
the  wounds  when  the  parasite  changes  its  position,  and  probably 
to  a  haemolytic  poison  which  the  parasite  produces.  Infestation  is 
without  an  intermediate  host.  The  eggs  in  water  or  in  moist  earth 
develop  into  embryos  which  may  be  swallowed,  or  when  they  come 
in  contact  with  the  skin  they  penetrate  this  and  enter  into  the 
lymphatics  or  blood  vessels.  Those  in  the  lymphatics  are  in  part 
retained  in  the  lymph  nodes,  in  part  carried  into  the  blood.  By 
means  of  the  blood  they  may  be  carried  into  the  lungs  from  which 
they  make  their  way  by  means  of  the  bronchi  and  trachea  into  the 
oesophagus  and  alimentary  canal. 

Flukeworms  or  Distomata,  the  most  important  of  these  to 
man  is  the  Schistosomum  Juzmatobium  (Distomum  hczmatobium 
Bilharzia).  The  sexes  are  separate,  the  male  thicker  and  somewhat 
shorter  than  the  female,  and  is  from  12  to  14  mm.  long  and  i  mm. 
broad.  The  sides  of  the  male  roll  forward  over  the  abdomen  to  form 
a  gynaecophorus  canal  in  which  the  female  is  carried.  The  mode  of 
infection  is  not  known;  the  parasite  settles  in  the  venous  system 
either  in  the  branches  of  the  portal  vein  or  in  the  veins  of  the  pelvic 
organs,  as  the  bladder  and  rectum.  The  ova  pass  from  the  vessels 
into  the  tissue,  where  they  produce  a  severe  inflammation  particu- 
larly when  they  enter  the  tissue  of  the  bladder.  They  may  produce 
hematuria;  urinary  fistulae  surrounded  by  large  masses  of  granula- 
tion and  cicatricial  tissue  may  perforate  the  scrotum  and  rectum. 
There  may  be  an  ascending  ^infection  leading  to  pyelonephrosis. 
On  miscroscopic  examination  the  ova  are  found  embedded  in  dense 
masses  of  cicatricial  tissue.  The  parasite  has  an  interesting  position 
in  view  of  the  frequency  of  the  development  of  papilloma  and  car- 
cinoma of  the  bladder  at  the  site  of  the  bladder  lesions  associated 
with  the  presence  of  ova. 

EXPERIMENTS.  The  experiments  in  infection  overlap  those  of 
inflammation  so  that  the  student  is  referred  to  those  on  the  latter 
subject  for  some  of  the  simpler  manifestations  of  infection  (see  p. 
58).  For  the  study  of  the  effects  of  diphtheria  bacilli  and  their 
toxin,  guinea  pigs  are  to  be  used.  Inject  subcutaneously  into  a 
guinea  pig  0.5  c.c.  24-hour  bouillon  culture  bacillus  diphtheria  and 
into  another  animal  2  units  of  diphtheria  toxin.  Observe  the  clini- 
cal course  of  the  condition  in  both  animals;  at  death  perform  autopsy 


PARASITIC  WORMS  335 

and  make  histological  and  bacteriological  examinations.  The  ex- 
periment is  made  additionally  interesting  by  protecting  other 
animals  by  the  use  of  anti-toxin.  Similar  experiments  with  bacillus 
dysenteriae  and  its  toxin  are  of  value  but  the  protecting  influence 
of  anti-toxin  is  so  slight  as  to  be  of  little  value  in  this  form  of  ex- 
periment. The  production  of  "  rat  typhoid"  by  the  subcutaneous 
injection  of  0.5  c.c.  24-hour  bouillon  culture  bacillus  murisepticus 
shows  interesting  lesions,  which  almost  duplicate  those  of  human 
typhoid.  The  special  lesion  of  pneumococcus  septicaemia  in  rab- 
bits is  best  studied  by  the  injection  of  0.5  c.c.  24-hour  neutral 
bouillon  culture  of  pneumococcus  into  the  posterior  auricular 
vein.  The  student  can  get  the  culture  by  injecting  pneumonic 
sputum  intraperitoneally  in  the  mouse  and  making  cultures  from 
the  heart's  blood.  The  same  culture  can  be  used  for  intrabron- 
chial  injection  into  the  dog  in  amounts  of  6  c.c.  The  dog  should 
be  killed  at  the  end  of  2  or  3  days  after  close  clinical  study  and 
the  autopsy  should  include  careful  histological  and  bacteriological 
study.  Tuberculosis  and  syphilis  present  interesting  experimental 
lesions.  Two  guinea-pigs  should  be  injected  intraperitoneally  each 
with  0.5  c.c.  salt  solution  suspension  human  type  tubercle  bacilli 
and  two  others  with  bovine  type  bacilli.  The  animals  are  to  be 
observed  clinically  until  death.  The  differences  in  clinical  course 
and  findings  at  autopsy  should  be  noted.  The  material  from  a 
chancre  or  moist  syphilitic  condyloma  should  be  injected  into  the 
testicle  or  under  the  skin  of  the  scrotum  of  a  rabbit.  With  the 
appearance  of  the  lesion,  smears  should  be  studied,  the  animal 
killed,  sections  of  the  testicle  studied  by  ordinary  histological 
methods  and  by  the  Ghoreyeb  and  Levaditi  methods  for  tissues. 


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335U1 


THE  PATHOLOGY  OF  THE  ORGANS  AND   TISSUES 
OF  THE   BODY 

INTRODUCTION 

Most  of  the  pathological  changes  in  the  individual  organs  and 
tissues  of  the  body  have  already  been  considered  in  the  various 
topics  discussed.  With  this  preceding  knowledge  and  with  certain 
things  held  clearly  in  mind,  the  pathology  of  the  organs  should 
present  little  difficulty.  It  is  important  to  bear  in  mind  (a)  the 
anatomy  of  an  organ,  this  including  topographical  relations,  gross 
form,  size,  mode  of  development  (the  last  particularly  as  affecting 
malformations),  circulation  and  histological  structure;  (6)  the 
physiology  of  the  organ,  hi  relation  to  the  body  as  a  whole  and 
whether  or  not  its  chief  function  is  excretory  or  secretory;  (c)  the 
infections  to  which  it  may  be  subjected,  including  resistance  to 
infection,  relations  to  the  outer  world  as  influencing  entry  of 
organisms,  the  relation  of  structure  to  internal  extensions  of  in- 
fection; (d)  the  character  of  the  degenerations  which  take  place, 
their  situation,  mode  of  origin  and  tissue  reactions;  (e)  the  capacity 
for  repair,  regeneration  and  hypertrophy;  (/)  the  tumors  both 
primary  and  secondary  which  may  develop.  While  there  is  a  close 
similarity  in  the  pathological  changes  in  all  the  organs  of  the  body, 
there  are,  however,  in  every  organ  certain  pathological  conditions, 
which,  like  the  organ  itself,  have  individual  characteristics.  These 
are  more  pronounced  in  the  kidney  than  hi  any  other  organ,  with 
the  possible  exception  of  the  central  nervous  system,  and  the 
pathology  of  the  kidney  will  be  considered  not  only  for  the  import- 
ance which  necessarily  attaches  to  the  organ,  but  that  the  descrip- 
tion may  serve  as  a  type  for  the  study  of  organic  disease. 


336 


THE   PATHOLOGY  OF  THE   KIDNEY 

DEVELOPMENT  AND  ANATOMY.  The  kidneys  are  paired  organs  of 
bean-shape,  the  combined  weight  in  the  adult  being  300  grams; 
they  are  deeply  placed  in  the  abdominal  cavity  behind  the  peri- 
toneum and  at  the  sides  of  the  lumbar  vertebrae.  They  lie  closely 
applied  to  the  diaphragm,  the  right  kidney  in  close  relation  with 
the  corresponding  adrenal  gland,  the  liver,  the  duodenum,  the 
hepatic  flexure  of  the  colon,  and  to  a  limited  extent  to  the  small 
intestine;  the  left  in  relation  to  the  adrenal  gland,  the  spleen,  the 
stomach,  the  pancreas,  the  splenic  flexure  of  the  colon  and  the  small 
intestine.  Each  kidney  is  closely  invested  by  a  fibrous  capsule. 
From  its  situation  the  kidney  is  well  protected  from  trauma,  and 
there  is  but  little  tendency  for  pathological  conditions  in  neighbor- 
ing organs  to  extend  by  continuity  into  the  kidney.  The  kidney 
has  a  complex  development  in  that  two  dissimilar  tissues  take  part 
in  the  formation  of  its  parenchyma.  The  ureter,  the  pelvis,  calices 
and  the  collecting  tubules  develop  by  an  outgrowth  from  the 
Wolffian  duct,  the  remaining  system  of  tubules  from  the  nephro- 
genic  tissue.  The  embryonic  development  is  not  completed  at 
birth  and  may  continue  up  to  the  second  year  of  life.  The  kidney 
contains  epithelial  tubules  which  pursue  a  tortuous  course  and 
which  in  their  course  present  differences,  in  the  character  of  the 
epithelium,  in  diameter  and  in  function.  The  tubules  have  an 
average  length  in  the  adult  kidney  of  5.2  cm.  and  begin  with  an 
expanded  end  into  which  a  mass  of  blood  vessels  projects  as  does 
the  heart  into  the  pericardial  cavity.  This  structure,  known  as 
the  glomerulus,  is  covered  by  a  syncytial  epithelium  continuous 
with  the  epithelium  of  the  tubules.  The  blood  vessels  of  the 
glomerulus,  which  in  size  resemble  capillaries,  are  divided  into 
small  groups,  the  epithelium  dipping  down  into  the  divisions 
between  the  groups.  The  vessels  are  lined  with  syncytial  endothe- 
lial  cells  containing  scattered  nuclei.  The  space  surrounding  the 
glomerulus  (the  subcapsular  space)  is  covered  with  low  epithelium; 
both  the  glomerular  and  the  capsular  epithelium  are  more  prominent 

337 


338  PATHOLOGY 

in  the  new-born  than  hi  the  adult.  From  the  capsular  space  there 
opens  a  tubule  convoluted  in  its  course  (the  proximal  convoluted 
tubule)  lined  with  large  epithelial  cells  without  distinct  cell  bound- 
aries. The  nuclei  are  near  the  basement  membrane  on  which 
the  cells  rest.  The  cytoplasm  is  granular,  the  granules  at  the  base 
of  the  cells  arranged  more  or  less  in  lines,  and  around  the  lumen 
there  is  a  brush-like  border  strongly  suggestive  of  cilia.  The  con- 
voluted tubule  changes  suddenly  into  the  descending  arm  of  the 
loop  of  Henle  hi  which  both  the  diameter  of  the  tube  and  the  lumen 
is  reduced  in  size;  the  epithelium  becomes  low,  the  cells  separated, 
the  tubute  resembling  a  capillary  lined  with  swollen  endothelium. 
The  tubule,  after  passing  toward  the  pelvis,  makes  an  abrupt  turn 
passing  back  towards  the  cortex  as  the  ascending  arm  of  the  loop 
of  Henle,  which  is  of  larger  diameter  and  lined  with  larger  and  more 
granular  epithelium.  The  ascending  limb  of  the  loop  passes  into 
a  second  or  distal  convoluted  tubule  which  lies  in  close  relation 
with  the  glomerulus  from  which  the  tubule  originated.  It  is  possible 
on  sections  of  the  kidney  to  distinguish  the  proximal  from  the  distal 
convoluted  tubule  by  the  larger  lumen  and  the  lower  and  clearer 
epithelium  of  the  latter.  The  distal  convoluted  tubule  passes  into 
the  collecting  tubule,  which,  after  dichotomus  joining,  opens  into 
the  pelvis  of  the  kidney  at  the  papilla. 

Certain  markings  are  recognized  on  section  passing  through  the 
kidney,  due  to  the  distribution  in  different  parts  of  the  kidney  of 
tubules  differing  in  structure.  Projecting  into  the  subdivisions 
of  the  pelvis,  the  calices,  are  the  rounded  extremities  of  the  pyra- 
mids. The  pyramids  are  triangular  in  shape,  are  paler,  more 
transparent  than  the  remaining  kidney  structure  and  show  distinct 
striae.  At  their  base  they  come  in  contact  with  the  cortex  and  the 
pyramidal  extensions  of  the  tubules  composing  them  (pyramids  of 
Ferrein)  project  into  the  cortex,  but  the  pointed  extremities  of 
the  latter  do  not  reach  the  surface  of  the  kidney.  Between  these 
pyramidal  extensions  are  the  convoluted  tubules  and  the  glomeruli, 
giving  the  tissue  here  a  more  opaque  and  granular  appearance. 
In  the  adult  kidney  the  glomeruli  can  be  distinguished  with  the 
naked  eye  as  fine  red  points.  The  tubules  of  the  kidney  are  sur- 
rounded by  a  membrana  propria  composed  of  fine,  resistant  fibres, 
reticulum,  which,  with  its  connections,  forms  a  continuous  frame- 
work throughout  the  organ.  This  is  more  abundant  than  elsewhere 


THE  PATHOLOGY  OF  THE  KIDNEY  339 

in  the  pyramids,  around  the  larger  vessels  and  about  the  glomeruli. 
Separating  the  pyramids  of  the  kidney  are  masses  of  cortex,  the 
columns  of  Bertini  which  pass  down  to  the  pelvis.  In  the  fcetal 
kidney  and  in  the  kidneys  of  certain  animals  the  organ  is  more  or 
less  subdivided  by  surface  depressions  into  a  number  of  units  termed 
renculi  each  of  which  comprises  a  pyramid  and  its  associated  cortex. 
In  the  adult  kidney  traces  of  these  sometimes  are  preserved. 

VASCULAR  SUPPLY.  The  renal  artery  breaks  up  into  a  number 
of  branches  which  pass  around  the  pelvis  and  before  entering  the 
kidney  each  divides  into  from  three  to  five  smaller  branches  which 
enter  the  kidney  at  the  side  of  the  papillae.  These  vessels  do  not 
anastomose,  each  supplying  a  definite  area  of  kidney  tissue.  On 
reaching  the  bases  of  the  pyramids  each  artery  breaks  up  into  a  series 
of  branches,  the  arcuate  arteries,  pursuing  generally  an  arched  course 
across  the  bases  of  the  pyramids.  From  these  arches  branches  are 
given  off  which  extend  to  the  cortex,  and  the  glomeruli  are  placed 
at  the  extremities  of  short  branches  given  off  from  these.  From 
the  arches  a  few  branches  (arteriae  rectae)  also  are  given  off,  which 
extend  into  the  pyramids.  The  arterial  branch  (vas  afferens) 
entering  into  the  glomerulus,  divides  into  from  four  to  six  branches 
each  of  which  breaks  up  into  bundles  of  capillaries  which  may  or  may 
not  anastomose.  These  masses  of  capillaries  produce  the  lobulated 
appearance  of  the  structure.  The  capillaries  unite  into  a  single 
vessel  (vas  efferens)  which  leaves  the  glomerulus  and  breaks  up 
into  a  rich  capillary  plexus  around  the  tubules.  The  blood  passes 
from  the  capillaries  by  three  routes.  The  capillaries  of  the  cortex 
pass  into  small  veins  beneath  the  surface  of  the  kidney  and  running 
parallel  with  it,  several  of  which  converge  at  a  single  point  making  a 
stellate  figure  (stellulae  Verheynii)  to  form  veins  which  pass  through 
the  cortex  in  company  with  the  corresponding  artery.  The  cortical 
capillaries  also  pass  into  small  branches  which  join  the  vein  as  it 
passes  through  the  tissue.  These  cortical  or  interlobular  veins  pass 
into  the  venous  arches  which  accompanying  the  corresponding 
arteries.  The  capillaries  of  the  pyramids  pass  into  straight  vessels 
(venae  rectae)  which  empty  into  the  arcuate  veins.  The  veins  in 
their  further  course  are  without  valves,  accompany  the  artery  and 
pass  into  the  vena  cava.  The  lymphatics  of  the  kidney  pass  into 
large  collecting  trunks  which  surround  the  renal  artery  and  dis- 
charge into  lymph  nodes  along  the  aorta  and  vena  cava.  The  blood 


34°  PATHOLOGY 

supply  of  the  kidney  is  relatively  great.  Although  the  kidneys 
form  but  0.56  per  cent  of  the  body  weight,  in  strong  diuresis  5.6 
per  cent  of  the  total  amount  of  blood  sent  into  the  aorta  in  a  minute 
may  pass  through  them. 

The  function  of  the  kidneys  is  wholly  excretory  and  nearly  the 
entire  nitrogen  elimination  takes  place  by  the  urine;  it  is  also  by 
means  of  the  kidney  that  toxic  substances  whether  formed  in  the 
body  or  introduced  from  without  are  removed,  and  in  the  process 
of  removal,  by  their  concentration,  may  produce  important  patho- 
logical conditions.  In  the  process  of  excretion  it  is  assumed  by 
most  authors  that  water  and  salts,  especially  urea  and  sodium 
chloride,  are  discharged  through  the  glomerulus  and  in  this  function 
blood  pressure  and  rapidity  of  stream  are  of  prime  importance. 
Various  substances  introduced  into  the  blood,  such  as  indigo  carmin, 
are  discharged  by  the  epithelium  of  the  convoluted  tubules  and 
may  be  demonstrated  in  the  epithelial  cells.  Methasmoglobin, 
when  present  in  the  blood,  is  also  so  discharged.  The  frequency 
with  which  degeneration  of  epithelium  limited  to  definite  areas  of 
the  tubules  is  met  with  is  in  favor  of  the  view  that  there  is  variation 
in  functional  activity  in  different  sorts  of  epithelium.  It  also  is 
generally  believed  that  the  urine  undergoes  a  concentration  in  its 
passage  through  the  tubules  by  water  absorption,  the  best  evidence 
for  this  being  the  concentration  of  albumin  to  form  casts  in  the 
Henle  loops,  and  the  formation  in  the  collecting  tubules  of  crystal- 
line products,  such  as  uric  acid. 

MALFORMATIONS.  The  most  common  and  the  least  important 
consist  in  the  retention  of  the  fcetal  lobulations  or  of  slight  depres- 
sions in  the  surface  indicating  this.  Congenital  displacements 
may  occur  and  the  dystopic  organ  lies  abnormally  low  either  over 
the  sacroiliac  junction  or  in  the  pelvis.  In  these  cases  the  kidney 
usually  is  malformed,  flattened  anteroposteriorly,  the  pelvis  turned 
to  the  front,  and  the  artery  given  from  the  lower  part  of  the 
aorta  or  from  the  iliac  artery.  Usually  but  one  kidney  is  displaced, 
the  left,  and  the  malformation  is  more  common  in  males.  Both 
kidneys  may  be  on  the  same  side,  one  below  the  other,  the  lower 
sometimes  overlapping,  sometimes  united  with  the  upper.  The 
lower  poles  may  be  joined  together  across  the  vertebral  column 
forming  a  single  horseshoe-shaped  organ,  but  with  two  pelves  and 
ureters,  and  the  vessels  may  show  variations  in  number  and  origin. 


THE  PATHOLOGY  OF  THE  KIDNEY  341 

In  all  these  variations  in  position  the  adrenal  glands  preserve  their 
normal  relations.  Great  importance  is  to  be  attached  to  the  im- 
perfect development  or  the  absence  of  one  kidney.  In  the  greatest 
degree  of  hypoplasia  the  kidney  is  represented  by  a  mass  of  bean- 
size  with  pelvis  and  attached  ureter.  Microscopically,  tubules 
without  glomeruli  are  found  in  the  structure,  the  malformation 
being  due  to  lack  of  development  on  the  part  of  the  nephrogenic 
tissue.  In  other  cases  the  organ  is  larger  and  contains  glomeruli 
and  tubules,  together  with  a  relatively  large  amount  of  connective 
tissue.  The  blood  vessels  are  correspondingly  small  and  may  have 
an  abnormal  origin.  It  is  not  impossible  that  certain  of  these 
hypoplastic  kidneys  may  result  not  from  malformation  but  from 
intra-uterine  atrophy  due  to  insufficient  vascular  supply.  Hypo- 
plasia or  aplasia  of  the  kidney  is  more  common  in  men  than  in 
women.  The  remaining  kidney  shows  compensatory  hypertrophy. 
Among  the  important  malformations  are  the  congenital  cystic 
kidneys  which  are  due  to  the  lack  of  junction  between  tubules 
which  are  developed  from  the  Wolffian  ducts  and  those  which  are 
developed  from  the  nephrogenic  tissue,  and  the  accumulation  of 
fluid  in  the  latter.  In  marked  degrees  of  this  malformation  enor- 
mous organs  filled  with  a  multitude  of  smaller  and  larger  cysts  are 
produced,  the  size  of  which  may  form  an  impediment  to  the  delivery 
of  the  foetus.  The  cysts  always  contain  constituents  of  the  urine; 
their  contents  may  be  clear  or  variously  discolored  by  the  admixture 
of  blood  pigment  from  slight  haemorrhages  into  the  cysts,  or  cloudy 
from  products  of  degeneration  of  the  lining  epithelium;  many  of 
the  cysts  contain  colloid  and  mucin.  There  is  increase  hi  connective 
tissue  in  the  walls  of  the  cysts,  but  there  may  be  no  interference 
with  the  function  of  the  kidney.  These  pronounced  cases  of  cystic 
kidney  frequently  are  associated  with  malformations  elsewhere. 
There  are  transitions  between  these  cystic  kidneys  and  the  presence 
of  solitary  cysts  which  may  be  as  much  as  8  cm.  in  diameter  and 
which  have  a  similar  origin. 

MALFORMATIONS  OF  URETERS.  One  of  the  most  frequent  mal- 
formations of  the  ureters  is  the  double  ureter  with  or  without 
doubling  of  the  pelvis  and  appearing  on  one  or  both  sides  (page  367). 
The  ureter  from  the  double  pelvis  may  unite  before  the  entrance 
into  the  bladder,  or  the  separation  may  be  complete.  Malformation 
of  the  ureter  may  take  the  form  of  narrowing,  or  closure,  which 


342  PATHOLOGY 

occurs  at  the  places  of  anatomical  narrowness,  at  the  origin  from 
the  pelvis  and  before  entering  the  bladder.  In  the  former  case  the 
narrowed  ureter  is  given  off  at  an  angle  high  up  in  the  pelvis  of  the 
kidney,  which  becomes  greatly^dilated,  congenital  hydronephrosis. 
A  sharp  angle  at  the  origin  of  the  ureter  may  give  rise  to  hydro- 
nephrosis without  any  narrowing  of  the  tube. 

Regeneration  and  hypertrophy  of  the  kidney  have  already  been 
considered  (page  129). 

THE  NOMENCLATURE  of  the  pathology  of  the  kidney  is  confusing. 
The  lesions  are  varied  both  in  extent  and  in  character,  and  com- 
plexities arise  due  to  the  complexity  of  both  structure  and  function. 
Regarding  the  essential  anatomical  units  of  the  kidney,  as  the  glom- 
eruli  and  the  tubules,  the  one  or  the  other  may  be  chiefly  affected 
which  would  make  possible  an  anatomical  classification  and  nomen- 
clature, but  in  numerous  conditions  both  are  affected  to  the  same 
degree.  The  relations  of  tubules  and  glomeruli  make  this  unavoid- 
able, the  tubule,  in  addition  to  its  specific  excretory  function, 
serving  as  the  duct  of  the  glomerular  gland  and  when  the  latter  is 
destroyed  the  tubule  undergoes  atrophy.  In  the  same  way  de- 
struction of  tubules  entails  destruction  of  the  related  glomeruli. 
There  is,  however,  justification  in  considering  certain  of  the  glom- 
erular lesions  as  a  unit,  from  the  fact  that  they  are  primary  and  the 
pathological  changes  similar  in  character.  A  better  nomenclature 
is  one  based  on  aetiology,  but  apart  from  the  fact  that  the  aetiology, 
especially  of  the  chronic  lesions,  is  obscure,  the  same  aetiological 
factor  in  different  degrees  of  intensity  and  with  a  difference  in  the 
associated  lesions  in  other  organs,  can  produce  various  conditions 
in  the  kidney.  The  kidney,  being  the  great  organ  of  elimination, 
is  easily  injured  in  the  discharge  of  toxic  substances;  in  the  infec- 
tious diseases  there  may  be  lesions  which  are  due  to  the  presence  of 
the  infectious  agents  and  lesions  mainly  degenerative  in  character, 
which  are  due  to  the  action  of  toxins  formed  elsewhere.  The  term 
nephritis  (inflammation  of  the  kidney),  with  a  preceding  descriptive 
adjective,  has  been  hitherto  generally  adopted  to  designate  lesions 
of  the  kidney  whatever  their  character.  All  lesions  in  the  body,  so 
far  as  they  comprise  the  result  of  injury  and  the  resulting  reaction 
of  the  tissues,  might  be  termed  inflammation;  but  the  use  of  the 
term  inflammation  has  become  limited  to  describe  those  lesions  in 
which  the  formation  of  an  exudate  is  the  leading  characteristic.  If 


THE  PATHOLOGY  OF  THE  KIDNEY 


343 


this  criterion  be  adopted,  the  term  cannot  be  applied  to  many  of  the 
pathological  conditions  in  the  kidney.  Bright,  an  English  physician 
in  1827,  described  a  pathological  condition  of  the  kidney  associated 
with  dropsy  and  albuminuria  and  the  name  Bright's  disease  has 
since  been  used  in  an  indefinite  manner  by  both  physicians  and  laity 
to  signify  pathological  conditions  in  the  kidney  whether  they  are  or 
are  not  associated  with  dropsy  and  albuminuria.  There  is  at 
present  a  tendency  to  substitute  for  nephritis  the  term  nephropathy 
which  signifies  disease  of  the  kidney,  with  a  preceding  adjective  or 
clause  descriptive  of  the  special  anatomical  or  aetiological  feature, 
and  this  usage  will  be  adopted  here. 

VASCULAR  NEPHROPATHY,  i.e.,  disease  of  the  kidney  due  to  dis- 
turbance in  the  circulation.  Acute  hyperamia  of  the  kidney  occurs 
in  increased  functional  activity  and  as  a  part  of  many  pathological 
conditions,  but  in  itself  leads  to  no  alteration  in  structure.  The 
condition  is  well  shown  in  acute  cases  of  poisoning  by  corrosive 
sublimate  and  arsenic.  The  kidney  is  swollen,  the  capsule  tense, 
the  color  an  intense  red,  the  glomeruli  easily  visible,  and  blood  drips 
on  section.  Passive  hyperamia  (chronic  passive  congestion)  occurs 
when  there  is  obstruction  to  venous  outflow  due  either  to  a  local 
or  central  cause.  The  kidney  is  large,  heavy,  of  a  dark  or  blue-red 
color  and  the  consistency  increased.  On  section  the  pyramids  are 
cyanotic  and  the  venae  rectae  appear  as  prominent  blue-red  streaks; 
the  glomeruli  are  easily  seen  as  bright  red  points.  Histologically, 
there  is  slight  degeneration,  and  often  atrophy  of  the  epithelium, 
increase  in  the  interstitial  tissue  which  may  take  the  form  of  thicken- 
ing of  the  membrana  propria  and  the  glomerular  capsules,  or  occur 
in  foci  associated  with  greater  degrees  of  atrophy.  The  glomeruli 
are  large,  the  vessels  distended  with  blood  and  not  infrequently 
red  blood  corpuscles  are  found  in  the  capsular  spaces  and  in  the 
tubules.  A  few  hyalin  casts  are  found  in  the  tubules,  and  after 
boiling  a  slight  albuminous  coagulum  in  the  capsular  spaces  and  in 
tubules.  The  estimation  of  the  effect  of  passive  congestion  is 
made  difficult  by  the  frequent  presence  of  conditions  due  to  other 
factors.  Passive  congestion  rarely  is  due  to  local  interference  with 
the  circulation.  Sudden  closure  of  the  renal  vein  produces  intense 
congestion  and  haemorrhage,  but  the  closure  by  thrombus  formation 
or  by  tumor  growth  in  the  vein,  produces  little  or  no  result,  the 
blood  passing  from  the  kidney  by  collateral  channels. 


344  PATHOLOGY 

Infarction  following  arterial  closure  is  more  common  in  the  left 
than  in  ihe  right  kidney  due  to  the  more  obtuse  angle  of  its  artery 
with  the  aorta.  The  form  and  size  of  the  infarct  depends  upon  the 
character  of  the  occluded  artery.  When  an  arcuate  artery  is 
occluded  near  its  origin,  the  infarction  is  large,  very  irregular  in 
outline  and  embraces  both  cortex  and  pyramid.  The  infarct  may  be 
confined  to  the  cortex  and  be  more  or  less  rectangular  in  shape. 
The  healing  of  the  infarcted  area,  which  takes  place  by  organization, 
leads  to  depressed  cicatrices  in  which  hyalin  masses  representing 
the  glomemli  are  seen.  There  is  no  regeneration. 

Hamorrhage  frequently  takes  place  in  the  kidney  and  may  be  the 
single  or  the  most  prominent  lesion.  It  may  take  place  from  the 
intertubular  vessels,  or,  as  usually  is  the  case,  from  the  glomeruli. 
The  haemorrhages  appear  as  small  red  foci  most  numerous  in  the 
cortex.  In  cases  where  the  haemorrhage  is  extensive,  the  presence 
of  the  blood  in  the  straight  tubules  gives  rise  to  red  streaks  on  section. 

A  special  type  of  nephropathy  has  been  described  in  connection 
with  arterio-sclerosis,  but  without  reason.  Arterio-sclerosis  may,  in 
two  ways,  produce  lesions  in  the  kidney;  (i)  by  local  interference 
with  nutrition  as  when  single  arteries  are  affected  chiefly,  foci  of 
atrophy  being  produced;  (2)  by  more  general  arterial  disease 
affecting  the  nutrition  of  the  entire  organ  and  producing  diffuse 
lesions.  The  arteries  of  the  kidney  must  be  regarded  as  among  the 
vessels  most  susceptible  to  arterio-sclerosis,  and  may  be  affected  in 
cases  in  which  there  is  but  little  evidence  of  arterial  change  in 
other  organs.  It  is  difficult  to  estimate  the  role  which  arterial 
disease  plays  as  a  single  factor  in  the  production  of  the  associated 
renal  lesions;  a  large  number  of  other  factors  may  play  a  part  such 
as  the  injurious  action  of  substances  derived  from  defective  metab- 
olism, the  associated  high  arterial  pressure  and  frequent  associa- 
tion of  passive  congestion. 

OBSTRUCTIVE  NEPHROPATHY.  (Hydronephrosis.)  Obstruction 
to  the  urinary  outflow  may  be  produced  in  several  ways.  The 
ureters  are  long  thin-walled  tubes  and  the  lumen  can  be  constricted 
by  pathological  conditions  arising  within  them  or  by  pressure  from 
without.  Obstruction  to  discharge  from  the  bladder,  occurring 
particularly  in  man,  quickly  distends  the  ureters.  Calculi  formed 
in  the  pelvis  of  the  kidney  may  become  impacted  in  the  ureter,  this 
generally  taking  place  at  the  entrance  into  the  bladder.  External 


THE  PATHOLOGY  OF  THE  KIDNEY  345 

pressure  on  the  ureter  is  more  common  in  women  owing  to  the 
greater  frequency  of  tumors  of  the  pelvic  organs,  and  approximately 
balances  the  effect  of  urethral  disease  in  the  male.  The  obstruction 
gives  rise  to  dilatation  of  the  pelvis  of  the  kidney  and  atrophy  of 
the  organ  (hydronephrosis) .  Complete  obstruction  is  rare.  The 
greatest  degree  of  hydronephrosis  is  seen  in  the  congenital  cases  in 
which  the  ureter  is  inserted  high  up  in  the  pelvis  of  the  kidney  and 
emerges  at  an  acute  angle.  The  condition  usually  is  bilateral.  The 
pelvis  of  the  kidney  may  be  converted  into  a  sac  containing  several 
litres  of  fluid  and  the  kidney  be  represented  by  a  thickened  area  of  the 
sac  wall  in  which,  on  microscopic  examination,  atrophic  glomeruli  and 
tubules  can  be  recognized.  In  less  marked  cases  the  calices  are  still 
present  and  the  atrophic  changes  are  most  evident  in  the  pyramids. 
The  atrophy  is  due  both  to  the  effect  of  pressure  on  the  epithelium 
and  to  anaemia  due  to  the  compression  of  the  vessels.  The  kidney 
is  always  paler  and  denser  than  normal;  microscopically,  there 
is  atrophy  and  degeneration  of  glomeruli  and  epithelium  and  a 
general  increase  in  the  interstitial  tissue  which  is  rich  in  elastic 
fibrils.  There  is  also  both  general  and  focal  infiltration  with  lym- 
phoid  cells.  By  infection,  which  readily  takes  place,  suppuration  of 
the  pelvis  and  kidney  may  be  produced,  converting  the  hydro- 
nephrosis into  a  pyelo-nephritis. 

The  formation  of  calculi  in  the  pelvis  of  the  kidney,  nephrolithi- 
asis,  is  due  to  the  precipitation  from  the  urine  of  uric  acid  or  salts. 
The  calculus  formation  is  assisted  by  products  of  inflammation  and 
degeneration,  forming  a  nucleus  on  which  the  sediment  accumu- 
lates. The  calculi  may  be  single  or  multiple  and  vary  in  size  from 
that  of  fine  sand  to  large  branching  structures  representing  casts  of 
the  entire  pelvis  and  calices.  The  formation  may  take  place  in 
single  calices. 

INFECTIOUS  NEPHROPATHY.  The  infectious  lesions  of  the  kidney 
are  focal  and  the  organisms  may  reach  the  organ  by  the  blood  or 
urinary  tract,  the  lesions  in  the  different  cases  showing  anatomical 
variations.  The  pelvis  may  share  in  the  infection,  pyelo-nephritis . 
The  types  of  the  infections  of  the  kidney  are  those  by  the  pyogenic 
organisms  and  by  the  tubercle  bacillus;  these  have  already  been 
considered. 

DEGENERATIVE  NEPHROPATHY.  Degeneration  of  the  epithelium 
of  the  kidney  is  found  in  all  types  of  lesions  and  may  constitute  the 


346  PATHOLOGY 

only  injury  apparent.  Most  forms  of  degeneration  which  occur  in 
man  may  be  produced  experimentally  in  animals.  The  degenera- 
tion may  affect  to  an  almost  equal  degree  all  parts  of  renal  paren- 
chyma or  be  confined  to  certain  areas  in  the  tubules.  In  many 
cases  the  degeneration  in  the  kidney  seems  merely  to  share  in  the 
general  degeneration  of  the  tissue  due  to  the  circulation  of  an 
injurious  substance,  in  others  the  degeneration  is  so  much  more 
marked  in  the  kidney  that  we  must  assume  either  a  greater  vulner- 
ability of  the  cells  of  the  kidney,  as  compared  with  other  organs,  or 
a  concentrated  action  of  the  agent  such  as  is  associated  with  its 
elimination.  It  is  known  that  arsenic  and  other  substances  are 
excreted  by  the  kidney  and  in  diphtheria  the  specific  toxin  is  found 
in  the  urine.  Degeneration  in  general  is  most  marked  in  the 
epithelium  of  the  convoluted  tubules,  which  is  in  accord  with  their 
known  secretory  activity. 

Normally,  the  human  kidney  contains  no  fat  demonstrable  by 
microscopic  methods,  the  comparatively  large  amount  of  fat  which 
chemical  methods  show  being  so  combined  with  protein  as  to  be  in- 
capable of  demonstration  by  other  than  chemical  methods.  The 
fat  which  normally  is  present  in  the  kidney  of  the  cat  is  confined 
to  the  convoluted  tubules  and  the  ascending  division  of  Henle's  loop. 
In  fatty  degeneration  (see  page  29)  of  the  human  kidney  the  fat  may 
have  either  a  systematic  or  irregular  distribution.  In  the  former  it 
may  be  confined  to  the  glomerular  epithelium,  to  that  of  the  con- 
voluted, Henle  or  collecting  tubules.  It  often  is  present  in  consider- 
able amount  in  the  epithelium  of  tubules  which  in  chronic  disease 
undergo  compensatory  hypertrophy.  In  arterio-sclerosis  the  fat 
may  be  irregular  in  distribution  owing  to  the  varying  degree  of  the 
affection  in  different  arteries.  In  the  infections,  also,  fat  may  have 
a  focal  distribution,  the  degeneration  being  associated  with  the  focal 
action  of  the  infectious  agent.  The  fat  is  in  small  granules,  gener- 
ally near  the  basal  border  of  the  cells,  may  constitute  the  only  ap- 
parent alteration,  or  may  be  associated  with  advanced  alterations, 
complete  necrosis  and  desquamation.  Rarely,  it  may  occur  in  large 
masses,  the  affected  cells  resembling  fatty  liver  cells.  Macroscopi- 
cally,  the  presence  of  fat  gives  rise  to  a  general  pallor  and  greater 
opacity  either  of  the  entire  kidney  or  of  the  areas  of  irregular  dis- 
tribution. In  cloudy  swelling  (see  page  29),  the  cells  are  swollen 
and  the  granulation  more  evident  than  normal.  The  condition  is 


THE  PATHOLOGY  OF  THE  KIDNEY  347 

always  most  evident  in  the  convoluted  tubules,  but  not  confined  to 
these.  It  often  is  associated  with  other  evidences  of  injury,  such  as 
broken  or  irregular  contour  of  the  cells,  desquamation  and  abnormal 
nuclear  staining.  The  condition  underlying  this  visible  alteration 
in  the  cells  is  unknown,  as  for  example,  whether  it  represents  an 
increase  in  number,  swelling  or  other  change  in  the  normal  granules, 
or  precipitation  in  granular  form  of  substances  previously  in  solu- 
tion. Alone  it  probably  represents  a  slight  degree  of  cell  injury. 
Closely  related  to  this  is  the  formation  of  large,  round  hyalin 
droplets  in  the  cells,  associated  with  great  swelling  and  disintegra- 
tion, in  consequence  of  which  the  hyalin  material  may  accumulate 
in  large  masses  within  the  tubules.  The  degeneration  is  a  serious 
one  and  is  confined  to  the  proximal  convoluted  tubules.  It  occurs 
in  those  forms  of  nephropathy  in  which  the  glomeruli  are  affected 
chiefly.  In  amyloid  degeneration  (see  page  31),  the  amyloid  sub- 
stance is  deposited  chiefly  around  the  vessels.  It  is  associated 
with  other  forms  of  degeneration,  particularly  the  hyalin  degenera- 
tion of  the  convoluted  tubules,  and  when  formed  rapidly  and  in  the 
absence  of  atrophic  and  sclerotic  conditions  of  the  kidney,  produces 
a  very  characteristic  macroscopic  appearance.  The  kidney  is  very 
large,  in  the  adult  the  combined  weight  often  reaching  600  grams. 
It  is  pale,  the  stellate  veins  prominent;  on  section  the  cortex  is 
greatly  swollen,  the  markings  obscure,  and  there  usually  are  foci  of 
opacity  due  to  the  presence  of  fat.  The  increased  size  is  due  to  a 
combination  of  epithelial  swelling,  dilatation  of  tubules  and  inter- 
stitial oedema  and  the  general  pallor  to  the  inhibition  of  the  cir- 
culation brought  about  by  the  deposit  of  amyloid  in  the  walls  of  the 
vessels,  particularly  in  the  glomeruli. 

Various  substances  may  be  excreted  by  the  kidney  in  such 
amounts  as  to  be  insoluble  in  the  urine  and  deposited  in  the  tissue. 
The  best  example  of  this  is  seen  in  the  uric  acid  infarction  of  chil- 
dren. This  occurs  almost  regularly  in  the  kidneys  of  children 
newly  born  or  a  few  weeks  old,  more  rarely  in  the  first  years  of  life 
and  very  rarely  in  adults.  In  this  condition  there  are  closely  set 
golden  yellow  streaks  in  the  pyramids  due  to  the  deposit  in  the 
papillary  ducts  of  round  or  irregular  granules  of  uric  acid  which 
often  show  concentric  or  radiate  markings.  In  these  cases  uric 
acid  in  sand-like  particles  may  be  present  in  the  pelvis  or  in  the 
calices.  In  cases  of  gout  there  may  be  deposits  of  needle-shaped 


348  PATHOLOGY 

crystals  of  urate  of  soda,  the  crystals  radiating  from  an  apex  which 
points  in  the  direction  of  the  pelvis.  The  masses  often  are  sur- 
rounded by  necrotic  tissue  and  giant  cells.  In  jaundice  of  newly 
born  children  (icterus  neonatorum)  there  may  be  crystalline  de- 
posits of  bile  pigment  in  the  pyramids  of  the  kidney,  bilirubin 
infarction,  which  simulate  the  uric  acid  deposits  but  are  of  deeper 
red  color.  In  jaundice  of  adults  there  is  always  fatty  degeneration 
due  to  the  toxic  action  of  bile  salts,  which  may  reach  a  high  degree 
and  be  associated  with  other  forms  of  degeneration  and  necrosis. 
The  general  green-yellow  color  of  the  kidney  is  due  to  the  diffusion 
of  the  bile  coloring  in  the  tissue,  but  in  addition  to  this  the  micro- 
scopic examination  shows  granular  masses  of  pigment  in  the  epi- 
thelial cells  and  contained  in  the  lumina  as  casts.  The  pigment 
also  is  found  in  the  epithelial  cells  of  the  glomerulus  and  capsule 
showing  that  it  is  excreted  in  part  at  least  by  this  structure.  In 
haemoglobinaemia  the  dissolved  haemoglobin  is  excreted  by  the 
kidneys  and  appears  in  the  urine  (haemoglobinuria,  methaemoglo- 
binuria).  The  excretion  takes  place  through  the  epithelium  of  the 
convoluted  tubules  which  contain  beaded  masses  of  haemoglobin 
easily  recognized  on  eosin  staining,  and  the  same  material  is  found 
in  the  lumina.  The  presence  of  the  haemoglobin  gives  macroscopi- 
cally  a  rusty  brown  color  to  the  cortex  with  brown  streaks  in  the 
pyramids  due  to  haemoglobin  casts  in  the  collecting  tubules.  As 
elsewhere  hi  the  body  necrotic  tissue  in  the  kidney  can  become  calci- 
fied, but  it  is  not  common.  It  takes  place  especially  in  the  necrosis 
of  epithelium  which  is  produced  by  poisoning  with  corrosive  subli- 
mate. In  cases  of  increased  lime  absorption,  particularly  in  old 
individuals,  circumscribed  foci  of  lime  salt  deposit  may  appear  in 
the  cortex  associated  with  necrosis.  Associated  with  all  these  con- 
ditions there  may  be  a  greater  or  less  degree  of  necrosis.  Save  in 
the  case  of  the  circumscribed  areas  of  necrosis  seen  in  the  infections 
and  in  infarction,  this  takes  place  in  the  direction  of  the  tubules. 
The  necrotic  cells  may  show  various  changes  due  to  degeneration 
preceding  necrosis,  or,  as  in  the  infarction,  a  rapid  necrosis  may 
produce  but  little  change  in  the  appearance  of  the  cells.  Often 
single  cells  in  the  course  of  a  tubule  show  necrosis.  Desquamation 
of  degenerated  and  necrotic  epithelium  takes  place  in  varying  degree 
and  the  castoff  cells  appear  hi  the  urine  often  in  such  numbers  that 
the  term  desquamative  nephropathy  has  been  used  to  distinguish 


THE  PATHOLOGY  OF  THE  KIDNEY  349 

such  cases.  After  death  changes  in  the  kidney  take  place  quickly, 
and  in  handling  or  sectioning  the  kidney,  the  epithelium  of  the 
collecting  tubules  may  become  exfoliated  in  large  masses  and  appear 
in  the  lumen  as  a  convoluted  mass  of  adherent  columnar  epithelial 
cells  and  be  mistaken  for  a  pathological  condition. 

ALBUMINTJRIA  AND  CASTS.  The  most  constant  clinical  evidence 
of  pathological  conditions  in  the  kidney  is  given  in  the  presence  of 
albumin  in  the  urine,  although  there  may  be  extensive  alteration  in 
the  kidneys  without  albumin  and  the  albumin  in  the  urine  may  come 
from  elsewhere  than  the  kidney.  It  is  probable  that  its  presence, 
even  hi  the  cases  of  the  so-called  physiological  and  in  the  transient 
albuminuria,  is  indicative  always  of  some  lesion  although  examina- 
tion may  not  reveal  it.  In  cases  of  albuminuria  when  the  kidney  is 
boiled  and  frozen  sections  made,  coagulated  albumin  is  found  in  the 
capsular  space  of  the  glomeruli  and  it  is  generally  assumed  that  the 
albumin  of  the  urine  has  entered  this  by  means  of  the  glomerulus. 
It  may,  however,  be  due  to  an  exudate  or  transudate  which  passes 
from  the  interstitial  tissue  into  the  tubules.  With  the  albumin 
structures  termed  casts  usually  appear  in  the  urine.  These  are 
cylindrical  hi  shape,  varying  somewhat  in  diameter  (n  to  22/1), 
and  are  composed  of  a  homogeneous  hyalin  material  often  con- 
taining other  substances.  The  hyalin  material  varies  in  appear- 
ance sometimes  having  such  slight  density 'and  refraction  as  to  be 
seen  with  difficulty,  at  others  it  is  dense,  refractive  and  the  casts 
often  show  fissures  as  though  produced  by  partial  fracture.  These 
two  sorts  of  hyalin  material  have  a  different  origin.  The  pale 
transparent  hyalin  casts  represent  albumin  which  has  become 
concentrated  by  absorption  of  water  in  passage  along  the  tubule 
and  has  undergone  some  form  of  colloid  change.  Elsewhere  hi 
the  body,  as  in  the  lungs,  hyalin  substances  of  this  nature  are 
found.  The  other,  more  refractive  form  of  cast  waxy  cast,  is 
formed  from  the  hyalin  globules  of  the  epithelium,  which  pass  into 
the  tubules.  This  form  of  cast  appears  in  the  urine  in  those  forms 
of  nephropathy  in  which  such  a  degeneration  occurs,  as  in  amyloid 
disease,  and  in  other  conditions  in  which  the  glomeruli  are  seriously 
affected.  In  passing  through  the  tubules  other  substances  can  be- 
come associated  with  the  hyalin.  Granular  casts  are  due  to  the 
mingling  with  the  hyalin  of  granules  coming  from  the  partial  or 
complete  disintegration  of  degenerated  cells.  Fatty  casts  are  due  to 


350  PATHOLOGY 

the  presence  in  the  hyalin  of  fat  from  cells  which  have  undergone 
fatty  degeneration.  Epithelial  casts  are  those  which  contain 
degenerated  and  desquamated  epithelial  cells.  Blood  casts  contain 
red  blood  corpuscles.  Fibrin  casts  are  those  in  which  threads  of 
fibrin  demonstrable  by  staining,  appear  when  there  is  a  fibrinous 
exudate  in  the  tubules.  The  presence  of  a  few  hyalin  casts  in  the 
urine  may  indicate  but  a  slight  degree  of  lesion  persisting  in  kidneys 
fully  adequate  for  function  and  the  casts  and  albumin  may  be 
absent  in  kidneys  in  which  incompetency  of  function  has  been 
produced  by  extensive  loss  of  parenchyma,  those  portions  of  the 
kidney  which  are  functioning,  but  inadequately,  being  normal. 

ACUTE  DIFFUSE  NEPHROPATHY.  The  degenerative  conditions 
which  we  have  been  considering  may  be  extensive  and  combined 
with  other  diffuse  lesions  consisting  in  vascular  changes  and  exudate 
formation;  but  these  affect  no 'part  so  specifically  as  to  warrant  a 
special  designation.  The  condition  is  relatively  rare,  for  apart  from 
the  infections  and  the  acute  interstitial  lesions  which  will  be  dis- 
cussed later,  acute  nephropathy  usually  is  glomerular  in  character. 
Certain  of  the  more  severe  degenerative  types,  associated  with 
haemorrhage  and  exudation,  which  are  seen  in  diphtheria,  belong  in 
this  class.  It  may  occur  also  in  typhoid  fever,  in  severe  malaria 
and  in  streptococcus  infection.  The  lesions  are  diffuse  and  vary  in 
character.  There  is  degeneration,  necrosis  and  desquamation  of 
epithelium,  with  oedema,  haemorrhage  and  cellular  infiltration,  in 
which  endothelial  cells  may  predominate,  in  the  interstitial  tissue. 
There  may  be  haemorrhage  and  even  a  fibrinous  exudation  from  the 
glomeruli,  with  necrosis  of  single  loops  of  vessels.  Macroscopically, 
the  kidneys  are  swollen,  the  markings  of  the  cortex  obscure. 

ACUTE  INTERSTITIAL  NEPHROPATHY.  This  is  the  most  common 
lesion  of  the  kidney  in  the  acute  infectious  diseases  of  children,  par- 
ticularly scarlet  fever  and  measles;  less  common  in  uncomplicated 
cases  of  diphtheria  and  in  smallpox.  In  adults  the  condition  is  more 
rare,  apparently  because  of  the  greater  rarity  of  the  diseases  with 
which  the  condition  in  the  kidney  is  associated.  Macroscopically, 
the  kidneys  are  swollen,  often  greatly  so,  pale  and  mottled  on  the 
surface,  on  section  moist,  opaque,  the  markings  obscure;  abundant 
cloudy  fluid  can  be  expressed.  The  entire  kidney  may  be  affected, 
or  the  lesions  have  a  more  focal  distribution  giving  rise  to  streaks 
of  opacity  in  the  cortex.  Microscopically,  the  lesion  consists  in 


THE  PATHOLOGY  OF  THE  KIDNEY  351 

infiltration  of  the  interstitial  tissue  with  large  mononuclear  cells  of 
an  indefinite  type,  often  closely  resembling  or  identical  with  plasma 
cells,  often  closely  resembling  myelocytes.  In  the  most  marked 
cases,  all  parts  of  both  cortex  and  pyramids  may  be  infiltrated  with 
these  cells;  in  less  marked  cases  the  foci  are  chiefly  in  the  upper 
portion  of  the  pyramid,  the  bordering  cortex  and  around  the  glom- 
eruli.  Some  of  the  large  mononuclear  cells  are  eosinophilic;  there 
are  also  phagocytic  cells  and  a  varying  number  of  polynuclear  leu- 
cocytes. In  the  capillaries  and  small  veins  numbers  of  similar  cells 
are  found,  and  the  source  of  the  cells  in  the  interstitial  tissue  is  by 
emigration  from  the  blood  vessels,  augmented  by  active  cell  divi- 
sion. The  large  mononuclear  cells  are  actively  amoeboid.  They 
may  be  found  in  the  walls  of  the  vessels  in  the  act  of  migration;  and 
in  the  interstitial  tissue  they  show  blunt  processes  and  other  mor- 
phological evidences  of  amoeboid  activity.  Numbers  of  cells  in 
nuclear  division  are  seen  both  hi  the  capillaries  and  among  the  inter- 
stitial cells.  The  presence  of  these  cells  in  the  interstitial  tissue  is 
not  in  association  with  epithelial  degeneration.  Degeneration  of 
the  epithelium  is  present,  but  not  more  marked  in  the  interstitial 
foci  than  elsewhere,  and  extensive  degeneration  and  necrosis  of 
epithelium  may  be  present  without  the  interstitial  changes.  Except 
in  the  most  marked  cases,  in  which  there  is  associated  destruction 
of  tissue,  the  interstitial  cells  do  not  enter  into  the  tubules  or  appear 
in  the  urine.  In  cases  in  which  these  interstitial  lesions  are  found, 
lesions  similar  in  character  often  are  found  in  the  heart,  adrenal 
glands  and  elsewhere.  There  are  no  lesions  in  the  glomeruli,  and 
although  similar  cells  may  be  found  within  the  glomerular  vessels 
they  do  not  migrate.  The  cell  accumulations  in  the  vessels  and 
interstitial  tissue  seem  to  depend  upon  changes  in  the  blood. 
Similar  cells,  in  the  diseases  concerned,  are  formed  in  the  spleen 
and  lymph  nodes,  from  which  organs  they  enter  the  blood.  They 
tend  to  accumulate  in  the  vessels  of  the  kidney  and  particularly  in 
those  of  the  pyramids.  The  great  numbers  of  cells  within  these 
vessels  shows  that  they  accumulate  there,  for  the  circulating  blood 
contains  no  such  numbers.  Whether  their  accumulation  is  due  to 
some  physical  condition  of  the  circulation  or  whether  there  is 
a  chemotactic  attraction  is  uncertain,  but  probably  the  latter  is  the 
case,  because  in  spleno-myelogenous  leukaemia  there  is  no  tendency 
for  the  blood  cells  to  accumulate  in  the  kidney. 


352  PATHOLOGY 

GLOMERULAR  NEPHROPATHY.  (Parenchymatous  nephritis.)  As 
has  been  said,  the  glomerulus  has  the  characteristics  of  a  gland, 
being  composed  of  vessels  membrana  propria  and  superimposed 
epithelium.  The  wall  of  the  capillaries  of  the  glomerulus  is  thicker 
and  more  refractive  than  the  walls  of  vessels  of  similar  size  else- 
where which  are  composed  of  cells  alone,  and  the  wall  stains  as 
does  the  membrana  propria  of  the  tubule.  The  embryonic  develop- 
ment of  the  glomerulus  by  the  ingrowth  of  vascular  loops  into  a 
tubule  lined  with,  epithelium  resting  on  membrana  propria  is  in 
favor  of  this  view  of  the  vessels,  as  is  the  further  fact  that  emigration 
of  leucocytes  does  not  take  place  through  the  glomerular  vessels 
save  in  unusual  conditions.  The  glomerulus  has  under  both  physio- 
logical and  pathological  conditions,  a  certain  independence  of 
position,  although  the  dependence  of  the  circulation  of  the  kidney 
on  the  integrity  of  the  glomerulus  causes  degenerative  lesions  of 
the  tubules  to  follow  lesions  of  the  glomerulus.  The  glomerular 
lesions  have  a  further  interest  in  that  certain  of  them  are  of  a 
character  which  is  not  met  with  elsewhere.  The  glomeruli  may 
form  the  initial  point  of  haematogenous  infection  of  the  kidney,  but 
such  infections  have  no  special  features.  Thrombi  due  to  conglu- 
tination of  red  corpuscles  are  found  more  frequently  in  the  glomeruli 
than  elsewhere,  for  which  no  explanation  is  available  The  lesions 
of  the  glomeruli  may  be  acute,  subacute  and  chronic,  with  a  very 
indefinite  separation  of  these  temporal  divisions.  The  causes  of  the 
essential  lesions  of  the  glomeruli  are  substances  in  solution  in  the 
blood  and  the  glomeruli,  being  equally  exposed,  all  are  affected  with 
but  little  difference  in  degree.  Such  substances  are  formed  in  the 
infections  and  there  is  a  close  relation  between  infectious  diseases 
and  glomerular  lesions.  In  certain  infections,  as  in  typhoid  fever, 
cerebrospinal  meningitis,  acute  pneumonia,  glomerular  nephropathy 
is  rare  and  it  occurs  more  frequently  in  association  with  endocardi- 
tis than  in  association  with  disease  of  any  other  organs. 

ACUTE  GLOMERULAR  NEPHROPATHY.  (Acute  parenchymatous  ne- 
phritis.) This  may  produce  but  little  macroscopical  alteration,  save 
slight  swelling.  On  close  examination,  however,  the  glomeruli  appear 
as  prominent  small  opaque  points,  in  very  marked  cases  the  section 
appearing  as  though  sprinkled  with  fine  sand.  On  microscopical 
examination  the  glomeruli  are  large  and  filled  with  cells.  The 
cells  have  two  sources.  In  one,  intracapillary  glomerulonephrop- 


THE  PATHOLOGY  OF  THE  KIDNEY 


353 


athy,  the  cells  are  contained  within  the  vessels.  In  certain  cases 
the  individual  cell  outlines  cannot  be  distinguished  and  the  cells 
appear  as  a  syncytium.  In  other  cases  most  of  the  cells  are  free 
within  the  capillaries.  They  are  of  an  endothelial  character 
which  is  apparent  both  from  their  appearance  and  from  the  presence 
of  nuclear  figures  in  the  endothelial  cells  of  the  vessels.  The 
newly  formed  cells  do  not  migrate  from  the  vessels.  Cases  may 
be  found  in  which  there  is  also  accumulation  of  polynuclear  leu- 
cocytes in  the  vessels  of  the  glomeruli  and  passage  of  both  these 
and  red  corpuscles  into  the  capsular  space.  The  accumulation  of 
cells  may  be  so  great  that  no  red  corpuscles  can  be  demonstrated 
within  the  tufts.  Necrosis  and  rupture  of  the  vessels  with  resulting 
haemorrhage  and  fibrin  in  the  capsular  spaces  also  may  take  place. 
The  other  source  of  the  cells  is  from  proliferation  of  the  epithelium, 
both  that  covering  the  vascular  tufts  and  lining  the  capsular  space, 
capsular  glomerular  nephropathy.  This  is  unlike  the  intracapillary 
form  since  it  does  not  occur  alone,  and  is  more  common  in  the  less 
acute  cases.  The  covering  cells  of  the  glomerulus  enlarge,  often 
forming  projecting  masses  of  cytoplasm  connected  with  the  vessels 
by  a  stalk,  and  extending  in  masses  between  the  tufts  of  vessels. 
The  proliferation  of  the  epithelium  lining  the  capsule  produces 
masses  of  flattened  or  crescent-shaped  cells,  the  individual  outlines 
of  which  often  are  indistinguishable.  In  sections  passing  through 
the  attachment  of  the  vessels  of  the  glomerulus,  the  cell  mass  in 
the  capsule  has  a  crescentric  shape,  and  in  sections  showing  a  part 
of  the  glomerulus  only,  they  appear  to  surround  the  mass  of  vessels. 
The  epithelium  of  the  tubules  is  degenerated,  often  desquamated 
to  a  considerable  extent  and  the  lumina  may  contain  desquamated 
cells  from  the  tubules  and  crescentric  cells  from  the  proliferated 
epithelium  of  the  glomerular  capsule.  However,  in  the  acute 
cases  of  this  form  of  nephropathy,  epithelial  degeneration  is  not  so 
prominent  as  in  many  of  the  more  strictly  degenerative  forms. 
In  the  interstitial  tissue  there  may  be  nothing  more  than  a  slight 
oedema. 

SUBACUTE  AND  CHRONIC   GLOMERULO-NEPHROPATHY.      (Chronic 

parenchymatous  nephritis.)  From  the  acute  there  is  a  gradual 
transition  to  the  chronic  forms,  in  which  atrophy  is  the  leading  char- 
acteristic. The  atrophy  ot  the  glomerulus  takes  place  by  hyalin 
degeneration  of  the  cells.  Even  in  the  acute  cases,  areas  in  the 


354  PATHOLOGY 

glomerulus  are  found  in  which  the  cell  outlines  are  indistinguishable ; 
in  chronic  lesions  this  increases  in  extent,  the  cells  gradually  be- 
coming converted  into  hyalin  masses,  the  nuclei  first  shrinking, 
and  finally,  for  the  most  part,  disappearing.  With  the  hyalin  for- 
mation and  due  probably  to  shrinkage,  the  lobulation  of  the  glomeru- 
lus becomes  more  evident,  it  being  converted  into  definite  hyalin 
lobes  separated  by  deep  depressions.  The  hyalin  material  stains 
as  does  the  connective  tissue,  but  it  is  not  fibrillar.  The  mass  of 
proliferated  capsular  epithelium  can  undergo  the  same  hyalin 
transformation,  but  in  this,  definite  connective  tissue  fibrils  appear, 
which  may  be  due  to  the  wandering  of  fibroblasts  into  the  cell 
mass,  or  what  appears  more  probable,  to  their  formation,  in- 
dependent of  cells.  The  epithelial  cells  in  the  capsule  are  often 
arranged  around  spaces  seemingly  representing  attempts  to  form 
tubules.  This  is  due  to  the  tendency  of  cells,  normally  lining 
spaces,  to  arrange  themselves  when  proliferating,  in  a  manner 
which  conforms  to  the  normal  type.  At  the  completion  of  the 
process  of  atrophy,  the  glomerulus  is  converted  into  a  mass  of 
hyalin  with  a  few  nuclear  remains  and  with  a  complete  absence 
of  vessels.  In  specimens  which  are  uninjected,  all  these  degrees 
of  glomerular  change  give  a  deceptive  impression  of  absence  of 
vessels.  The  kidneys  are  injected  with  difficulty  and  in  all  con- 
ditions the  circulation  within  the  glomerulus  is  greatly  impeded 
and  the  vessels  in  large  measure  occluded.  An  imperfect  circu- 
lation is  maintained  by  the  dilatation  of  short  loops  at  the  root 
of  the  glomerulus  forming  communication  between  the  afferent 
and  the  efferent  vessels,  and  by  new  communications  which  are 
formed  between  the  vessels  of  the  glomerulus  and  those  of  the 
capsule.  In  certain  cases  on  the  outside  of  the  hyalin  masses, 
numbers  of  intact  vessels  may  be  seen  which  probably  represent 
a  regenerative  new  formation.  Both  the  macroscopic  and  the 
microscopic  appearance  of  the  kidney  depends  upon  the  chronicity 
of  the  process  and  the  degree  of  atrophy.  In  the  less  chronic 
cases  the  kidney  is  enlarged  and  pale,  but  the  pallor  is  never  so 
marked  as  in  the  large,  white  kidney  of  amyloid  disease.  The 
combined  weight  may  vary  from  350  to  500  grams,  but  such  great 
enlargement  as  the  latter  figure  is  rare.  On  section  the  kidney  is 
firm,  the  cortex  swollen,  pale,  or  mottled,  the  markings  obscure 
and  the  tissue  more  moist  than  normal.  Microscopically,  the 


THE  PATHOLOGY  OF  THE  KIDNEY  355 

lesions  are  diffuse,  all  parts  of  the  cortex  being  equally  involved. 
The  most  marked  condition  of  the  epithelium  is  atrophy.  The  cells 
of  the  convoluted  tubules  lose  their  characteristics  and  are  con- 
verted into  a  low  epithelium.  The  tubules  are  dilated,  but  due  to 
the  atrophy  of  epithelium,  the  dilatation  is  more  apparent  than  real. 
The  pallor  is  due  to  anaemia  and  may  be  added  to  by  fatty  degenera- 
tion of  the  epithelium.  Hyalin  degeneration  of  the  epithelium  of 
the  proximal  convoluted  tubule  is  rarely  absent.  The  tubules  are 
more  widely  separated  by  oedema,  the  normal  injection  of  capillaries 
is  absent  save  in  foci.  There  is  little  or  no  increase  in  the  general 
connective  tissue  of  the  kidney  save  in  the  chronic  cases  where 
the  atrophy  is  more  extreme.  Where  the  glomeruli  are  completely 
destroyed  the  appertaining  tubule  is  collapsed;  it  may  be  repre- 
sented by  a  small  mass  of  atrophic  epithelium  or  totally  disappear. 
The  areas  of  connective  tissue  represent  for  the  most  part  areas  of 
complete  destruction  of  glomeruli  and  tubules.  In  the  chronic 
cases,  the  kidney  is  small,  always  rather  pale,  the  capsule  may  be 
adherent  and  the  surface  smooth  or  irregularly  roughened.  On 
section  both  cortex  and  pyramids  are  atrophic.  In  these  cases  the 
destruction  of  glomeruli  has  reached  an  extreme  degree.  Both  the 
macroscopic  and  the  microscopic  picture  of  these  kidneys  may  be 
affected  by  the  presence  in  the  kidney  of  lesions  to  which  those  of 
glomerular  nephropathy  are  superadded,  or  which  may  develop  in 
the  course  of  the  glomerular  disease.  In  adults  one  of  the  most 
frequent  complicating  conditions  is  arterio-sclerosis  with  its  ac- 
companying renal  lesions.  The  clinical  picture  of  glomerular 
nephropathy  is  nearly  as  characteristic  as  the  anatomical.  There 
is  usually  the  history  of  an  acute  onset  accompanying  or  following 
an  infection.  Certain  of  the  chronic  cases  in  the  adult  can  be  traced 
to  infection  in  childhood.  There  frequently  are  exacerbations  of 
the  disease  at  intervals.  The  urine  is  diminished  in  amount  and 
casts  of  all  varieties  are  abundant.  It  is  with  this  form  of  renal 
disease  that  dropsy  is  so  frequently  associated.  Obscure  as  is  the 
jetiology,  there  is  such  unity  in  character  of  the  glomerular  lesions 
that  it  seems  most  probable,  in  spite  of  the  number  of  different 
infections  with  which  the  process  is  associated,  that  one  single 
cause  must  be  operative. 

CHRONIC  DIFFUSE  NEPHROPATHY.     (Chronic  interstitial  nephri- 
tis;  granular  contracted  kidney;   gouty  kidney.)     As  is  apparent, 


356  PATHOLOGY 

by  the  various  synonyms,  a  dominant  feature  in  this  form  of 
nephropathy  is  atrophy  of  the  kidney.  The  capsule  usually  is 
thickened,  and  the  kidney  often  is  embedded  in  a  large  mass  of 
fat.  The  capsule  adheres  to  the  surface  in  places,  and  small 
portions  of  parenchyma  may  be  torn  off  with  it.  The  surface  may 
be  smooth,  but  usually  is  covered  with  small  elevations  which  vary 
in  size.  The  general  color  of  the  surface  usually  is  red  or  grayish 
red,  and  the  elevated  granules  are  redder  than  the  depressions 
between  them.  The  consistency  of  the  kidney  is  tough,  in  some 
cases  almost  like  leather.  On  section  the  atrophy  is  most  marked 
in  the  cortex.  The  markings  of  the  cortex  are  not  apparent  and 
the  differentiation  of  cortex  and  pyramid  not  so  evident  as  normally. 
Microscopically,  the  most  obvious  condition  is  atrophy  of  the 
parenchyma  with  a  marked  increase  in  the  connective  tissue.  The 
areas  of  atrophy  correspond  to  the  gross  depressions  on  the  surface. 
On  section  these  are  triangular  in  shape,  the  apex  pointing  toward 
the  pyramid.  The  depressed  areas  may  appear  as  little  more  than 
scars,  in  which  the  tubules  have  disappeared  and  the  glomeruli,  as 
small  hyalin  masses,  persist  in  the  cicatricial  tissue.  The  number 
of  cells  in  the  interstitial  tissue  varies  greatly.  In  the  most  marked 
foci  and  beneath  the  capsule,  there  frequently  is  an  intense  infil- 
tration with  lymphoid  cells.  Elsewhere  throughout  the  kidney, 
particularly  in  the  vicinity  of  the  veins,  such  areas  of  lymphoid  in- 
filtration may  be  prominent.  Cysts  are  numerous  and  vary  in  size, 
sometimes  apparent  on  microscopic  examination  only,  and  filled 
with  stiff  colloid  material.  Towards  the  pyramids  the  collecting 
tubules  often  are  dilated  and  may  have  a  spiral  course  due  to  con- 
traction of  the  tissue.  There  is  a  minor  degree  of  atrophy  and 
interstitial  increase  in  the  areas  which  correspond  to  the  surface 
elevations.  Not  infrequently  intact  glomeruli  larger  than  the 
normal,  some  of  them  reaching  275  p,  in  diameter,  are  seen,  and  in 
association  with  them  are  found  convoluted  tubules  of  greater 
diameter,  and  greater  length,  lined  with  large  epithelial  cells. 
Such  areas  are  to  be  attributed  to  compensatory  hypertrophy  of 
both  tubules  and  glomeruli.  Hyalin  casts  are  frequent  in  all  the 
divisions  of  the  tubules.  A  varying  degree  of  fatty  degeneration 
always  is  present  together  with  very  marked  atrophy  of  the  epithe- 
lial cells,  and  in  places  there  is  necrosis.  In  the  more  atrophic 
areas  of  the  kidney,  collapsed  tubules  or  tubules  containing  remains 


THE  PATHOLOGY  OF  THE  KIDNEY        357 

of  epithelial  cells  can  be  distinguished.  The  process  of  atrophy 
is  different  in  glomerular  nephropathy,  although  the  final  result 
is  the  same;  the  atrophy  of  glomeruli  in  diffuse  nephropathy  often 
appears  to  be  concentric  and  due  to  a  gradual  sclerosis  and  thicken- 
ing of  the  capsule.  In  most  cases,  however,  the  vessels  of  the 
glomeruli  show  a  hyalin  thickening  usually  not  diffuse,  but  in 
foci,  and  more  apparent  in  the  centre  of  the  glomerulus  than  else- 
where. This  takes  place  with  no  increase  in  the  number  of  cells. 
Occasionally,  kidneys  are  found  in  which  the  lesions  are  less  ad- 
vanced and  in  which  the  thickening  of  the  vessels  of  glomeruli  is 
the  most  marked  feature.  The  size  of  the  kidney  may  give  but 
little  indication  of  the  degree  of  atrophy.  The  atrophy  may  be 
concealed  by  hyperplasia  of  the  fat  of  the  pelvis  which  takes  the 
place  of  the  renal  tissue.  Chronic  diffuse  nephropathy  is  essentially 
a  disease  of  individuals  past  the  middle  life.  Very  rarely  the  con- 
dition is  encountered  under  the  age  of  twenty-five  years  and  may 
even  be  seen  in  children,  but  in  these  cases  the  condition  is  one  of 
minor  degree. 

ASSOCIATED  CONDITIONS.  The  anatomical  picture  which  the 
kidney  presents  can  be  complicated  by  the  association  of  other 
conditions  such  as  amyloid,  extreme  degrees  of  acute  degeneration, 
and  acute  and  chronic  glomerular  changes.  The  essential  condi- 
tions in  the  kidney  are  degeneration,  atrophy,  connective  tissue 
increase  and  contraction.  The  degree  of  actual  increase  of  con- 
nective tissue  is  difficult  to  estimate.  Frequently  in  the  place 
of  definite  fibrillar  connective  tissue,  a  hyalin  material  is  formed 
which  stains  as  does  connective  tissue.  Such  material  is  found 
more  frequently  in  the  pyramid  of  the  kidney  than  in  the  cortex. 
The  connective  tissue  seems  to  represent  more  the  collapsed  frame- 
work of  the  organ  than  an  actual  new  formation. 

ARTERIO-SCLEROSIS  OF  KIDNEY.  The  most  striking  single  con- 
dition in  the  kidney  is  that  affecting  the  arteries.  Arterio-sclerosis 
of  the  larger  vessels  is  almost  universally  present.  The  efferent 
vessels  of  the  glomeruli  show  hyalin  thickening  of  the  walls  which 
can  lead  to  complete  closure.  The  changes  in  the  glomeruli  them- 
selves seem  to  be  of  much  the  same  character  as  the  arterio-sclerotic 
changes.  The  vascular  lesions  of  the  kidney,  are,  however,  so  much 
more  pronounced  in  these  cases  than  vascular  lesions  in  other  organs, 
that  it  is  difficult  to  say  whether  they  should  be  regarded  as  primary 


PATHOLOGY 

or  as  associated  lesions.  That  the  condition  is  not  entirely  depen- 
dent on  arterio-sclerosis  is  evident  from  the  fact  that  it  may  be 
found,  although  rarely  and  in  minor  degrees,  in  cases  before  the 
arterio-sclerotic  age  is  reached  and  in  which  the  connective  tissue 
increase  seems  simply  to  follow  degeneration  and  destruction  of 
tubules.  The  condition  is  essentially  chronic  and  usually  only 
advanced  cases  are  seen.  It  is  not  preceded  as  are  the  glomerular 
cases  by  acute  stages.  The  clinical  picture  has  always  been  recog- 
nized as  differing  from  the  glomerular  nephropathy.  The  urine  is 
increased  in  amount.  Albumin  is  present,  but  the  amount  is 
usually  not  great.  Heart  hypertrophy  and  increased  blood  pressure 
is  almost  uniformly  present.  (Edema  is  not  usually  present,  but 
there  may  be  associated  cardiac  oedema  due  to  dilatation  and  in- 
sufficiency of  the  heart.  The  condition  on  the  whole  is  not  so 
unfavorable  as  is  the  glomerular  nephropathy  owing  to  the  fact  that 
the  lesions  are  not  so  diffuse  and  that  the  destruction  of  parenchyma 
can,  to  a  certain  extent,  be  compensated  by  hypertrophy  of  both 
glomeruli  and  tubules.  The  closely  related  senile  nephropathy  has 
already  been  considered. 

A  CASE  or  CHRONIC  GLOMERULAR  NEPHROPATHY 

Anatomical  Diagnoses.  Chronic  glomerular  nephropathy;  Healed 
operation  wound  (decapsulation  of  kidney);  Anaemia;  Hyper- 
plastic  bone  marrow;  Peritoneal  adhesions;  Slight  hypertrophy 
of  heart;  Slight  arterio-sclerosis;  Malnutrition;  Slight  oedema 
of  face. 

Clinical  history.  Scarlet  fever  at  one  year  of  age  and  whooping  cough 
at  four.  Was  first  seen  by  a  physician  July  10,  1905.  For  one  year  had 
had  oedema,  headaches,  loss  of  appetite,  debility,  pallor,  and  had  lost 
weight.  On  July  18,  1905,  by  operation  through  loin,  both  kidneys  were 
decapsulated.  The  capsule  of  the  kidney  was  found  thin  and  the  kidney 
under  no  tension  whatever.  They  were  nearly  twice  the  normal  size, 
mottled  and  yellowish  in  color.  A  piece  of  the  kidney  removed  at  this 
time  showed  a  subacute  glomerular  nephropathy.  Convalescence  was 
easy  and  operation  led  to  improvement  of  all  conditions.  For  two  years 
after  the  operation  there  was  no  oedema  of  the  face  and  only  slight  oedema 
of  legs.  Appetite  also  improved,  and  all  bodily  functions  seem  good. 
Complexion  continued  pale  with  a  tinge  of  yellow.  Two  years  after 
operation  condition  gradually  became  worse.  There  was  general  weak- 


THE  PATHOLOGY  OF  THE  KIDNEY  359 

ness,  loss  of  appetite,  oedema  of  legs,  but  not  of  face,  nausea  and  vomiting. 
Toward  the  end  there  were  convulsions,  in  one  of  which  she  died.  Death 
took  place  March  10,  1908,  two  years  and  eight  months  after  the  opera- 
tion. The  urine  examination  showed  before  the  operation  a  daily  amount 
of  1440  c.c.m.,  of  high  color,  slight  trace  of  chlorides,  specific  gravity  1014, 
acid  reaction,  |  per  cent  albumen,  large  amount  of  sediment  in  which 
were  various  sorts  of  renal  epithelium,  most  of  them  fatty,  large  hyalin 
and  granular  casts  and  some  blood.  After  the  operation,  the  urine 
diminished  temporarily,  but  gradually  rose  in  about  six  months  to 
2000  c.c.m.  which  was  continued  until  towards  death  when  the  amount 
was  again  reduced.  The  casts  were  always  present  and  there  was  always 
albumen.  Three  weeks  after  operation  there  was  only  a  trace,  but  this 
increased  in  amount  and  in  six  months  it  regained  the  former  \  per  cent. 

White,  female,  age  seventeen  years.  The  body  small,  slightly  built, 
nutrition  poor.  No  palpable  lymph  nodes.  The  general  surface  of  body 
pale.  In  each  lumbar  region  there  is  an  oblique  linear  scar  of  the  old 
operation  wound,  each  10  cm.  in  length.  The  scar  begins  3  cm.  below 
the  costal  margin,  5  cm.  from  median  line  and  extends  obliquely  down- 
wards and  outwards.  Scanty  development  of  axillary  and  pubic  hair. 
There  is  slight  oedema  of  face  and  eyelids,  no  oedema  of  extremities  or 
trunk.  The  subcutaneous  fat  small  in  amount  and  very  yellow. 

Diaphragm  in  usual  position.  Little  fat  in  great  omentum.  Mesen- 
teric  lymph  nodes  visible,  but  not  enlarged.  The  appendix  10  cm.  long 
and  free  from  adhesions.  The  bladder  is  distended.  It  fills  the  pelvis 
and  reaches  to  a  point  midway  between  umbilicus  and  pubis.  A  dense 
band  of  adhesions  extends  from  the  posterior  parietal  peritoneum  over 
the  right  kidney  to  the  inferior  surface  of  the  right  lobe  of  the  liver,  3  cm. 
to  the  right  of  the  gall  bladder.  There  are  no  adhesions  elsewhere. 
There  is  no  free  fluid  in  the  peritoneum.  The  intestines  are  collapsed. 

The  pleural  cavities  dry  and  free  from  adhesions. 

The  pericardium  normal.  Over  the  epicardium  of  the  right  ventricle 
there  is  a  small  opaque  patch  of  pericardial  thickening. 

Heart,  weight,  275  grams.  The  right  side  is  dilated  with  fluid  blood, 
the  left  is  firmly  contracted.  On  section  the  myocardium  is  pale  and 
of  normal  consistence.  Endocardium  and  valves  normal.  Coronary 
arteries  normal. 

The  lungs  are  normal.    There  is  no  oedema. 

Liver  weighs  1400  grams.  The  surface  is  smooth  except  for  a  band  of 
adhesions  mentioned.  The  lobules  of  the  liver  distinct. 

The  gall  bladder  is  thin-walled  and  contains  50  c.c.  of  dark  fluid  bile. 

Spleen  weighs  70  grams.    Normal. 

Pancreas  normal. 


360  PATHOLOGY 

Gastrointestinal  canal  normal. 

Adrenals  normal. 

The  kidneys  of  the  same  size,  general  appearance  the  same.  The 
right  kidney  is  surrounded  with  dense  tissue  containing  small  quantities 
of  fat  enclosed  in  dense  connective  tissue.  Beneath  this  the  organ  has  a 
nodular,  rough  surface;  the  capsule  is  very  thick.  It  strips  with  some 
difficulty  owing  to  adhesions  with  the  kidney  and  leaves  a  coarsely 
granular  surface.  The  kidney  is  pale,  opaque,  with  very  small  white 
foci.  On  section  the  general  cut  surface  is  pale,  but  the  middle  is  slightly 
darker  than  the  cortex.  The  average  measurement  of  the  cortex  is 
3  mm.,  and  on  section  the  glomeruli  stand  out  prominently  as  pale  or 
pink  dots.  They  are  more  prominent  and  larger  than  normal.  There 
are  irregular  areas  and  streaks  of  pale  yellow  opacities  which  are  especi- 
ally marked  at  the  bases  of  the  pyramids,  the  streaks  often  extending 
into  these.  The  cortex  shows  a  fine  mottling  owing  to  the  presence  of 
pale,  opaque,  slightly  yellow  areas.  The  pelvis  is  small  and  contains  a 
small  amount  of  fat;  the  mucous  membrane  pale.  The  renal  artery  is 
of  small  calibre.  The  ureters  small  and  collapsed.  Then*  mucous  mem- 
brane, as  well  as  that  of  the  bladder,  is  pale  and  smooth.  Genitalia 
normal. 

Throughout  the  aorta  there  are  discrete,  slightly  elevated  patches 
which  are  more  opaque  than  the  general  intima.  This  is  especially 
marked  about  the  commencement  of  the  intercostal  vessels. 

Bone  marrow  is  hyperplastic  and  of  light  pink  color. 

Microscopical  examination  of  the  kidney  stained  for  fat  shows  an 
irregular  distribution  of  this.  The  largest  amount  is  present  in  foci  of 
convoluted  tubules.  The  fat  is  in  both  the  epithelium  and  in  the  in- 
terstitial tissue.  There  is  fat  also  present  in  the  glomeruli.  In  the 
completely  hyalin  glomeruli  there  is  a  small  amount  of  fat  in  very 
minute  granules  in  the  hyalin  material.  Other  glomeruli  show  fat  in 
the  thickened  capsular  epithelium. 

A  section  of  the  kidney  through  the  capsule  showed  a  greatly  thickened 
capsule  composed  of  cicatricial  connective  tissue  containing  but  few  cells, 
the  fibres  of  which  intermingle  with  the  connective  tissue  of  the  kidney. 
The  glomeruli  are  all  greatly  enlarged.  Most  of  them  show  the  same 
condition.  On  measurement  they  vary  from  275  to  350  p.  in  diameter. 
Most  of  them  are  larger  than  this.  As  a  rule,  they  do  not  completely 
fill  the  capsular  space  which  contains  a  considerable  amount  of  granular 
material.  The  capsules  are  thickened.  A  number  of  the  glomeruli  are 
small,  completely  'atrophic,  forming  hyalin  masses  which  have  fused 
with  the  greatly  thickened  and  hyalin  capsule.  There  is  every  grada- 
tion between  these  completely  hyalin  glomeruli  and  glomeruli  which 


THE  PATHOLOGY  OF  THE  KIDNEY  361 

show  a  development  of  hyalin  within  the  vascular  tufts  and  a  thickened 
but  nonadherent  capsule.  Occasionally,  there  are  adhesions  and  vascu- 
lar connections  between  the  tuft  of  blood  vessels  and  the  capsule.  The 
lobulation  of  the  glomerulus  is  much  more  distinct.  In  each  one  there 
are  large  single  tufts  of  vessels  which  vary  in  size,  the  divisions  extending 
down  to  the  origin.  In  sections  stained  with  the  connective  tissue  stain, 
there  is  general  thickening  of  the  walls  of  the  vessels  in  these  tufts  and  in 
places  a  complete  substitution  of  hyalin  connective  tissue  for  the  vessels. 
The  nuclei  are  increased  in  number,  the  hyalin  material  often  contains 
great  numbers  of  nuclei.  There  are  numbers  of  leucocytes  contained 
within  the  vessels  of  the  glomeruli  which  are  still  pervious,  but  the  general 
cellular  increase  is  in  the  form  of  larger  cells  with  nuclei  of  endothelial 
character.  There  is  a  varying  degree  of  capillary  obliteration.  In 
many  of  the  glomeruli  the  vessels  immediately  on  the  periphery  bordering 
the  capsule  are  pervious,  their  walls  of  ordinary  character  and  contain 
red  blood  corpuscles. 

The  proximal  convoluted  tubules  in  places  have  a  high  granular 
epithelium  containing  hyalin  droplets.  Foci  of  convoluted  tubes  are 
found  which  are  dilated  and  lined  with  granular  epithelium.  Casts  are 
numerous  in  all  of  the  varieties  of  tubules.  The  interstitial  tissue 
generally  is  increased  in  amount.  The  membrana  propria  of  the  least 
altered  tubules  are  thickened  and  in  places  there  are  large  areas  composed 
almost  entirely  of  connective  tissue.  Closer  examination  of  these  areas 
shows  in  the  midst  of  the  masses  of  connective  tissue  atrophied  tubules 
represented  by  not  more  than  a  few  cells.  Most  of  the  apparent 
connective  tissue  increase  seems  to  be  relative  and  due  to  atrophy  and 
destruction  of  parenchyma.  There  are  great  numbers  of  cells  in  the 
atrophied  tissue. 

REMARKS.  In  this  case  there  is  a  history  of  acute  infection  at 
an  early  age.  The  date  and  the  character  of  the  onset  of  the  acute 
nephropathy  is  uncertain.  There  may  have  been  an  acute  attack 
coincident  with  the  scarlet  fever  or  whooping  cough,  with  partial 
recovery  and  exacerbation,  or  the  nephropathy  may  have  been 
independent  of  this.  It  is  of  great  interest  that  the  operation 
enabled  the  condition  of  the  kidney  to  be  ascertained  nearly  three 
years  before  death.  This  operation  is  for  two  purposes:  (i)  To 
relieve  a  supposed  condition  of  increased  tissue  pressure  within  the 
kidney  by  splitting  the  capsule;  (2)  To  increase  the  circulation 
within  the  kidney  which  is  obstructed  by  the  glomerular  changes 
by  causing  a  closer  connection  between  kidney  and  capsule  with 


362  PATHOLOGY 

anastomosis  between  the  capsule  vessels  and  the  renal  capillaries. 
There  is  no  doubt  that  the  adhesions  between  capsule  and  kidney 
in  condition  of  chronic  nephropathy  may  provide  increased  circu- 
lation. In  this  case  it  seems  to  have  done  good.  The  convulsions 
of  the  patient  which  preceded  death  were  uraemic  and  the  exact 
relation  of  such  convulsions  to  the  nephropathy  is  imperfectly 
understood.  There  was  a  slight  degree  of  heart  hypertrophy,  and 
the  oedema  which  was  so  evident  during  the  course  of  disease  had 
almost  disappeared  at  the  time  of  death. 


A  CASE  OF  INTRACAPILLARY  GLOMERULAR  NEPHROPATHY 

Anatomical  Diagnoses.  Intracapillary  glomerulo-nephropathy;  Ana- 
sarca  (general);  Hydrothorax  (double);  Ascites;  Congestion 
and  oedema  of  lungs;  Arterio-sclerosis  (moderate);  Fatty  liver 
(slight);  (Edema  of  brain. 

White,  male,  forty-six  years  of  age.  Body  well  developed  and  well 
nourished.  Rigor  mortis.  There  is  very  marked  oedema  of  face  and  in 
a  less  degree  of  the  extremities.  The  conjunctivas  oedematous.  The 
subcutaneous  tissues  are  oedematous  throughout. 

Peritoneal  cavity.  The  peritoneum  is  somewhat  thicker  than  nor- 
mal and  contains  yellow  fat;  is  quite  cedematous.  The  cavity  con- 
tains 1000  c.c.  of  fluid.  The  appendix  is  4  cm.  in  length,  has  a 
mesentery  to  its  tip  and  is  directed  to  the  right  along  the  lower  wall  of 
the  caecum. 

Pleural  cavities.  Each  cavity  contains  1000  c.c.  of  a  clear,  straw- 
colored  fluid.  Otherwise  they  are  negative. 

Pericardial  cavity.     Contains  100  c.c.  of  a  clear,  straw-colored  fluid. 

Heart.  Weight,  430  grms.  It  is  firmly  contracted.  The  edges  of 
the  mitral  valve  are  slightly  thickened  and  cedematous.  The  myocar- 
dium is  somewhat  softer  and  more  moist  than  normal.  The  coronary 
arteries  show  some  sclerosis  about  their  orifices,  and  a  slight  sclerotic 
change  along  the  first  cubic  centimeter  of  their  course.  There  appears 
to  be  a  slight  oedema  of  the  myocardium. 

Lungs.  They  show  quite  marked  oedema  and  congestion,  the  former 
being  most  prominent. 

Spleen.  Weight,  130  grams.  Surface  is  smooth.  Organ  is  flabby, 
cut  surface  is  light  red. 

Gastro-intestinal  tract.    Normal. 

Pancreas.    Normal. 


THE  PATHOLOGY  OF  THE  KIDNEY         363 

Liver.  Weight,  1800  grams.  Surface  is  smooth  and  on  section  it 
is  a  light  reddish  brown  with  pale  yellowish  mottling. 

Kidneys.  Weight,  620  grams.  Capsule  nonadherent.  Color  of  sur- 
face pale  gray,  opaque  with  occasional  small  deep  red  foci  not  over 
i  mm.,  generally  less  than  this,  in  diameter.  The  stellate  veins  injected 
and  prominent.  On  section  the  cortex  shows  a  few  diffusely  scattered 
red  points.  The  markings  are  obscure  or  not  visible.  The  color  is  pale, 
with  areas  of  marked  opacity.  It  is  more  moist  than  is  the  normal  cortex. 
The  average  width  of  cortex  is  i  cm.  Over  the  section,  the  glomeruli 
are  visible  as  opaque  points.  They  project  above  the  section,  but  cannot 
be  felt.  Occasionally,  they  are  injected  and  stand  out  as  red  points. 
The  pyramids  are  of  normal  size,  pale  red  in  color. 

Adrenals.    Are  surrounded  by  fat.    Otherwise  negative. 

Bladder  negative. 

Genital  organs.  There  is  marked  oedema  of  the  scrotum.  The  tu- 
bules of  testicles  strip  easily. 

Aorta.  Shows  slight  thickening  which  occurs  in  yellowish  bands 
running  in  the  direction  of  the  course  of  vessels. 

Head.  Brain,  weight,  1375  grams.  Scalp  is  covered  by  a  good 
growth  of  iron  gray  hair.  The  tissues  of  the  scalp  are  enormously 
swollen  with  fluid.  Calvarium  is  normal.  The  pia  arachnoid  contains 
a  large  amount  of  fluid.  There  is  slight  opacity  at  numerous  points, 
especially  along  the  lines  of  vessels.  Vessels  at  base  show  numerous 
areas  of  sclerosis,  and  on  section  remain  wide  open.  Lateral  ventricles 
contain  a  few  cubic  centimeters  of  clear  fluid.  Tissues  of  brain  are 
cedematous. 

Middle  ears  normal. 

The  histological  examination  of  the  kidneys  showed  the  glomeruli 
enlarged,  for  the  most  part  apparently  bloodless,  the  large  size  being  due 
to  filling  of  the  vessels  with  cells  having  vesicular  nuclei.  The  covering 
epithelium  is  swollen  and  shows  in  places  large  projecting  cells  attached 
to  the  surface  by  a  process.  The  intertubular  tissue  is  dilated,  and  con- 
tains foci  of  haemorrhage  corresponding  with  the  red  points  mentioned. 
The  epithelium  of  the  tubules  is  swollen  and  degenerated,  that  of  the 
proximal  convoluted  tubules  often  containing  hyalin  globules. 

REMARKS.  Nothing  is  known  as  to  the  history  of  this  case. 
The  renal  lesions  are  typical. 

EXPERIMENTS.  Experimentally  hydronephrosis  is  best  produced 
in  the  cat  by  aseptic  ligation  of  a  ureter  under  deep  ether  anaesthesia, 
the  autopsy  being  performed  three  weeks  later.  The  experiment  can 


364  PATHOLOGY 

be  repeated,  injecting  into  the  pelvis  0.5  c.c.  24-hour  bouillon  culture 
colon  bacillus  so  as  to  produce  pyonephrosis,  the  autopsy  being 
performed  one  week  later.  Various  types  of  acute  experimental 
nephropathy  are  produced  by  injecting  into  rabbits  as  follows:  for 
tubular  nephropathy,  0.05  gram  potassium  chromate;  for  vascular 
nephropathy,  o.ooi  gram  cantharadin  in  acetic  ether;  interstitial 
nephropathy,  daily  injections  for  3  days  of  10.0  c.c.  i  :  1000  mercuric 
chloride  solution;  acute  nephropathy  with  edema,  o.ooi  gram  ura- 
nium nitrate  and  daily  administration  by  stomach  tube  of  50  to  100 
c.c.  water.  All  the  animals  are  kept  in  metabolism  cages  and 
daily  examinations  of  the  urine  made.  At  the  termination  of  2  or 
3  days  autopsies  are  performed  and  the  kidneys  and  other  organs 
studied  grossly] and  histologically.  Arsenic  nephropathy  (glomeru- 
lar)  has  to  be  studied  more  quickly,  the  urine  examination  and 
autopsy  being  made  within  an  hour  after  the  injection  of  o.oio  gram 
potassium  arsenate. 

For  the  studies  in  nitrogen  metabolism  a  cat  is  placed  on  a  meat 
diet  which  keeps  its  weight  constant,  the  non-protein  nitrogen  and 
urea  nitrogen  of  the  blood  being  determined  by  the  Folin  colorimet- 
ric  methods  on  several  occasions  for  purposes  of  control.  The  cat 
is  then  given  0.002  gram  uranium  nitrate  and  on  the  next  day, 
and  alternate  days  following,  the  nitrogen  determinations  made. 
Daily  urine  examinations  and  complete  autopsy  are  to  be  made. 
These  experiments  are  followed  by  a  demonstration  of  the  vascular 
reactions  of  dogs,  the  subjects  of  tubular  and  vascular  nephritis, 
by  the  kymographic  registration  of  kidney  volume,  blood  pressure 
and  diuresis. 


364  a 


364  b 


364  c 


364  d 


364  f 


364  g 


364  h 


3641 


364  j 


364k 


3641 


36401 


364  n 


3640 


364  p 


THE  PATHOLOGICAL  ANATOMY  OF  THE 
ALIMENTARY  CANAL 

From  the  importance  of  the  alimentary  canal  both  as  a  surface  of 
the  body,  thereby  in  close  relation  with  infection,  and  from  the 
anatomical  and  physiological  importance  of  its  structure,  there 
have  necessarily  been  numerous  inferences  in  the  preceding  chapters 
to  its  pathology.  There  are  two  anatomical  conditions,  however, 
which  have  received  no  attention.  Ulcer  of  the  stomach  (round 
ulcer  of  the  stomach,  peptic  ulcer),  differs  in  a  remarkable  way 
from  ulcers  in  other  tissues;  this  is  due  mainly  to  the  action  of  the 
gastric  juice.  Any  necrotic  tissue  in  the  stomach  is  removed  not 
by  the  ordinary  processes  of  histolysis  or  organization,  or  phago- 
cytosis, but  by  digestion.  Small  losses  of  substance  in  the  stomach 
not  extending  beneath  the  mucous  membrane,  often  are  associated 
with  superficial  liaemorrhages.  Both  the  effused  blood  and  the 
necrotic  mass  are  digested,  giving  rise  to  small  superficial,  circum- 
scribed losses  of  substance.  Such  haemorrhagic  "erosions"  seem 
to  have  no  relation  with  chronic  ulcers. 

The  chronic  ulcers  most  frequent  are  found  in  the  posterior 
wall  of  the  pyloric  portion  of  the  stomach,  or  at  the  junction 
of  this  with  the  cardia.  The  ulcer  is  usually  round,  but  may  be 
oval  or  pear-shaped.  The  edges  do  not  project.  The  base  and 
sides  are  clean,  sharp  and  free  from  necrotic  material.  The  base 
is  smaller  than  the  surface  and  the  sides  often  approach  the  base 
by  a  series  of  step-like  processes  (terraced  ulcer).  There  is  irregu- 
larity in  this,  however,  and  usually  one  side  of  the  ulcer,  that 
towards  the  pylorus  by  preference,  is  more  perpendicular.  The 
single  coats  of  the  stomach  often  appear  in  the  wall  as  though 
artificially  dissected.  The  appearance  of  the  ulcer  has  been  com- 
pared with  the  loss  of  substance  which  would  be  produced  by 
removing  a  portion  of  the  tissue  with  a  punch.  Microscopically, 
there  usually  is  absence  of  any  marked  inflammatory  change  in 
the  edges  or  base.  There  is  usually  a  thin  line  of  granulation 
tissue  on  the  surface  with  some  induration;  the  cells  on  the  surface 

365 


366  PATHOLOGY 

have  the  appearance  of  being  necrotic,  but  this  is  probably  a  pose 
mortem  change  due  to  the  action  of  the  gastric  juice.  The  arteries 
of  the  wall  of  the  stomach  in  the  immediate  vicinity  of  the  ulcer 
usually  are  obliterated  either  by  thrombosis,  by  entarteritis  and 
occasionally  by  embolus.  The  process  does  not,  however,  involve 
the  arteries  at  a  distance.  These  ulcers  may  be  single  or  multiple, 
and  ulcers  of  a  similar  character  may  be  found  in  the  duodenum. 
The  etiology  of  the  process  is  not  clear.  It  does  not  seem  to  have 
any  relation  with  arterio-sclerosis,  and  is  most  common  at  an  age 
prior  to  that  in  which  arterio-sclerosis  is  common.  The  condition 
is  more  common  in  women  than  in  men.  The  ulcers  may  produce 
various  results.  They  may  heal  with  extensive  formation  of 
cicatricial  tissue  and  stenosis  may  be  produced  by  the  contraction 
of  this,  particularly  when  the  ulcer  is  near  the  pylorus.  The  ulcer 
may  perforate  the  stomach,  in  some  cases  leading  to  acute  peri- 
tonitis; in  other  cases  when  adhesions  have  been  formed  with  the 
surrounding  tissue,  the  ulcer  may  extend  into  the  pancreas  or  into 
the  liver,  or  into  the  colon.  By  the  action  of  the  gastric  juice, 
necrosis  and  extensive  loss  of  substance  may  be  produced  in  neigh- 
boring organs  when  the  ulceration  extends  into  these.  Extensive 
and  fatal  haemorrhage  may  result  from  erosion  of  blood  vessels 
which  have  not  previously  become  occluded. 

APPENDICITIS.  This  is  the  most  common  serious  pathological 
condition  in  the  alimentary  canal,  and  one  of  the  most  common  of 
human  diseases.  In  its  general  histology,  .the  mucous  membrane 
of  the  appendix  resembles  that  of  the  large  intestine  with  the  im- 
portant difference  that  the  muscularis  mucosa  is  absent  and  that 
there  is  a  very  much  greater  development  of  lymphoid  tissue  in  the 
mucosa.  The  lymph  follicles  project  above  the  surface  and  the 
epithelium  dips  down  between,  forming  shallow  crypts.  The  whole 
structure,  particularly  the  proximal  end,  has  much  similarity  with 
that  of  the  tonsil. 

Acute  appendicitis  is  due  to  surface  infection.  In  the  earliest 
cases  examination  shows  a  small  loss  of  substance  of  the  surface 
usually  in  one  of  the  depressions  between  the  lymph  follicles.  At 
this  point  there  is  an  exudation  of  leucocytes  and  fibrin  which  lies 
partly  in  the  tissue  and  partly  projects  into  the  lumen.  Around  this 
there  is  intense  infiltration  of  leucocytes  which  often  extends  through 
the  entire  wall.  The  lumen  may  be  entirely  filled  by  a  purulent  ex- 


PATHOLOGICAL  ANATOMY  OF  THE  ALIMENTARY  CANAL     367 

udate.  The  process  may  heal  at  this  stage  or  extend  further,  result- 
ing in  ulcerative  appendicitis.  In  this  condition  the  purulent 
infiltration  is  more  extensive,  and  by  softening,  ulceration  is  pro- 
duced which  may  lead  to  perforation.  The  process  may  extend  into 
the  meso-appendix  producing  an  inflammatory  thrombosis  of  the 
veins  with  resulting  haemorrhagic  infarction  and  complete  necrosis  of 
the  appendix.  In  the  very  early  cases  there  may  be  but  little  change 
of  the  peritoneal  surface.  Later,  the  appendix  is  swollen,  red,  and  the 
serous  surface  covered  with  fibrinous  exudate.  The  uncomplicated 
acute  forms  may  recover  fully,  the  appendix  presenting  no  evidence 
of  previous  disease.  Where  the  ulceration  has  been  extensive, 
stenosis  and  complete  obliteration  may  result.  Following  oblitera- 
tion, secretion  may  accumulate  in  the  distal  end  forming  cysts 
(mucocale).  The  etiology  of  appendicitis  is  not  clear.  Foreign 
bodies,  especially  intestinal  concretions  which  so  frequently  are 
found,  probably  take  no  part  in  its  production.  Various  organisms 
may  be  obtained  from  cultures  in  the  acute  cases,  but  there  is  no 
reason  to  believe  that  these  are  other  than  secondary  invaders, 
and  in  the  most  acute  cases  organisms  may  be  absent. 


A  CASE  OF  ACUTE  APPENDICITIS  WITH  PERFORATION  AND 

ACUTE  PERITONITIS  ASSOCIATED  WITH  COLON 

BACILLUS 

Anatomical  Diagnoses.  Acute  appendicitis  with  perforation;  Gen- 
eral acute  peritonitis;  Myocarditis  (acute);  Congestion  and 
oedema  of  lungs  (lower  lobes);  Acute  splenic  tumor;  Sclerosis 
of  coronary  arteries;  Sclerosis  of  mitral  valve  (aortic  cusp); 
Chronic  adhesive  pleuritis  (right  side);  Papilloma  of  shoulder; 
Double  ureter  (unilateral.) 

White,  male,  age  sixty  years.  Body  well  developed  and  well  nourished. 
There  is  considerable  lividity  of  lower  limbs  and  of  the  back.  The  skin 
generally  is  dry  and  the  face  has  a  slight  icteroid  tint.  Situated  over 
the  upper  portion  of  the  right  shoulder,  there  is  a  small,  pedunculated 
tumor,  2.5  cm.  in  diameter.  Its  surface  consists  of  closely  packed,  dark- 
brown  papillary  processes.  This  tumor  is  attached  to  the  adjacent  skin 
by  a  small  pedicle.  The  abdomen  is  markedly  distended  and  tympan- 
itic;  there  is  no  oedema. 

Peritoneal  cavity.  Fat  is  well  developed  and  is  bright  yellow  in  color. 
When  the  peritoneum  is  cut  through,  considerable  amount  of  gas  escapes 


368  PATHOLOGY 

from  the  peritoneal  cavity.  The  intestines  are  everywhere  deeply 
injected,  and  show  varying  amounts  of  an  acute  exudate  upon  them. 
This  acute  exudate  consists  of  small  grayish-white  plaques  or  sheets  of 
considerable  size,  which  adhere  loosely  to  the  peritoneum  covering  the 
intestines.  The  coils  of  the  small  intestine  are  loosely  bound  together  by 
a  similar  exudate.  The  parietal  peritoneum  is  deeply  injected  throughout 
the  left  side;  the  anastomosis  of  the  smaller  vessels  stand  out  distinctly. 
The  parietal  peritoneum  shows  an  acute  inflammatory  reaction,  most 
marked  in  the  region  of  the  appendix.  The  upper  surface  of  the  liver 
is  coated  by  a  thin  layer  of  exudate.  The  abdominal  cavity  contains 
considerable  dark  colored,  foul  smelling  fluid;  this  is  most  marked  in  the 
pelvis.  While  the  peritoneum  everywhere  shows  acute  inflammatory 
reaction,  this  reaction  is  most  marked  in  the  region  of  the  caecum.  In 
this  latter  region,  the  coils  of  the  intestines  are  closely  adherent  and  are 
attached  to  the  overlying  parietal  peritoneum,  walling  off  an  area  which 
contains  a  considerable  amount  of  dark  colored,  foul  smelling  material. 
The  visceral  peritoneum  and  parietal  peritoneum  enclosed  in  this  area 
shows  a  much  more  marked  inflammatory  reaction  than  elsewhere 
throughout  the  abdomen.  In  the  former  area,  that  is  about  the  caecum, 
the  peritoneum  shows  very  marked  discoloration.  Its  blood  vessels  are 
deeply  injected.  The  intestines,  beginning  at  the  sigmoid  and  passing 
upward,  show  in  addition  to  the  acute  inflammatory  reaction  upon  their 
surface  no  lesions  until  the  caecum  is  reached.  The  caecum  and  the 
appendix  present  the  following  appearance.  The  appendix  measures 
about  8  cm.  in  length,  hangs  down  free  from  the  lower  portion  of  the 
caecum,  has  a  mesentery  to  its  tip,  laden  with  fat.  The  appendix  itself 
is  very  markedly  discolored,  swollen  and  soft;  is  easily  torn.  On  the 
border  opposite  the  mesenteric  attachment,  and  situated  3  cm.  from 
the  caecum,  there  is  a  circumscribed,  very  black  area  measuring  about 
6  cm.  in  diameter.  In  the  centre  of  this  area  there  is  a  small  opening 
3  mm.  in  diameter,  which  connects  directly  with  the  lumen  of  the  appen- 
dix, and  through  it  fecal  material  escapes  upon  pressure. 

Heart.  Normal  size.  Weight  331  grams.  The  valves  are  normal, 
except  a  small  area  in  the  aortic  cusp  of  the  mitral  valve,  in  which 
locality  there  is  a  circumscribed,  yellowish  area  of  thickening.  On 
section  the  myocardium  of  the  left  ventricle  shows  numerous  irregularly 
shaped,  very  pale,  somewhat  soft  areas,  which  stand  out  sharply  from 
the  surrounding  muscle  tissue.  These  areas  vary  from  pin  point  to 
2  or  3  mm.  in  diameter,  and  are  generally  most  numerous  in  the  outer 
half  of  the  muscular  wall,  though  a  few  are  seen  irregularly  distributed 
throughout  the  ventricular  wall.  The  right  coronary  artery  shows  an 
occasional,  small,  yellowish,  slightly  thickened  area.  The  left  coronary 


PATHOLOGICAL  ANATOMY  OF  THE  ALIMENTARY  CANAL     369 

artery,  about  3  cm.  from  its  beginning,  shows  upon  that  portion  of  the 
wall  which  rests  against  the  myocardium,  a  calcined  area  about  4  mm. 
in  length.  This  calcified  area  involves  not  more  than  one-half  of  the 
arterial  wall.  It  infringes  somewhat  on  the  lumen  of  the  vessel,  but  does 
not  occlude  it.  Throughout  the  remainder  of  this  coronary  artery, 
there  is  an  occasional  area  of  thickening,  but  no  calcined  areas. 

Lungs.  Crepitant  throughout.  Pleurae  are  generally  smooth  and 
glistening.  No  areas  of  consolidation  are  noted.  The  lower  surface 
of  the  middle  lobe  on  the  right  side,  and  the  upper  surface  of  the  lower 
lobe  on  the  same  side  are  loosely  bound  together  by  a  few  delicate  fibrous 
adhesions.  On  section  the  upper  lobes  are  moist  and  of  a  salmon-pink 
color.  The  lower  lobes  are  of  a  light  red  to  a  deep  red  color,  and  from 
their  cut  surfaces  a  large  amount  of  air-containing  blood-stained  fluid 
escapes. 

Spleen.  This  is  slightly  increased  in  size.  Weight  155  grams.  On 
section  the  pulp  is  brownish  gray  in  color  and  a  considerable  amount  of 
it  adheres  to  the  knife  blade. 

Liver.  Weight  1650  grams.  The  gall  bladder  is  slightly  distended. 
Its  walls  and  surrounding  tissues  are  deeply  stained  with  bile.  The 
cystic  and  common  bile  ducts  are  patent.  The  external  surface  of  the 
liver  shows  an  acute,  inflammatory  reaction.  On  section  the  paren- 
chyma is  of  a  yellow  color,  and  is  quite  soft;  the  liver  substance  just  be- 
neath the  capsule  is  very  dark  red. 

Pancreas.  Normal.  The  lesser  peritoneal  cavity  is  smooth  and 
glistening.  There  is  no  exudate  in  this  area. 

Kidneys.  Weight  305  grams.  They  are  embedded  in  a  large  amount 
of  firm  yellow  fat.  They  appear  normal  in  size.  On  section  the  cortex 
is  of  normal  thickness.  The  glomeruli  are  distinctly  visible  as  glisten- 
ing points.  The  ureter  on  the  left  side  is  normal.  Upon  the  right  side 
the  pelvis  of  the  kidney  has  opening  into  it  two  separate  ureters,  one 
going  to  each  pole  of  the  kidney.  These  ureters  open  into  separate 
pelves.  Throughout  10  cm.  of  their  course  this  double  ureter  exists, 
when  the  two  fuse  together  leading  to  a  ureter  of  normal  size. 

Adrenals  normal. 

Bladder  normal. 

Prostate  normal. 

Aorta.  Not  opened  on  account  of  the  undertaker  insisting  that  it  be 
undisturbed. 

Cover-slip  preparations  of  the  peritoneal  exudate  showed  a  variety 
of  organisms,  the  most  numerous  being  short  bacilli  [conforming  mor- 
phologically to  the  colon  bacilli  which  were  both  free  and  enclosed  in 
leucocytes. 


370  PATHOLOGY 

Microscopic  examination  of  the  small  foci  in  the  heart  showed  masses 
of  bacilli  similar  to  those  in  the  peritoneal  exudation  which  are  in  great 
part  within  widely  dilated  vessels  which  are  occluded  by  them,  and  in 
part  in  masses  in  the  tissue.  About  them  there  is  extensive  haemorrhage 
and  the  muscle  fibres  in  the  vicinity  are  necrotic,  and  for  the  most  part 
disintegrated.  Section  of  the  liver  with  the  peritoneal  exudation  on  the 
surface  shows  on  the  surface  of  the  liver  a  thick  meshwork  of  fibrin  filled 
with  polynuclear  leucocytes.  Above  this  the  exudation  contains  closely 
packed  leucocytes  and  but  little  fibrin.  Great  numbers  of  short  bacilli 
are  contained  in  the  polynuclear  cells  and  in  part  are  free. 

REMARKS.  The  acute  peritonitis  followed  perforation  of  the 
gangrenous  appendix.  The  lesions  of  the  heart  are  due  to  emboli  of 
bacteria,  the  embolism  taking  place  shortly  before  death,  and  the 
immense  numbers  of  organisms  present  is  probably  to  be  in  part 
attributed  to  post  mortem  growth.  The  tissue  reaction  is  shown 
by  the  necrosis  of  muscle  and  the  haemorrhagic  exudation.  The 
absence  of  leucocytes  is  remarkable.  This  may  be  due  to  several 
things;  to  the  draining  of  the  leucocytes  from  the  blood  by  the 
peritoneal  exudation  and  the  inhibition  of  leucocytic  hyperplasia 
by  the  toxaemia;  to  the  bacteria  having  acquired  such  virulence 
that  the  activity  of  the  leucocytes  were  inhibited.  The  malforma- 
tion of  the  kidney  consisting  in  separate  pelves  and  ureters  is  one 
of  the  most  common  types  of  malformation.  In  this  type  the 
double  ureter  more  generally  continues  into  the  bladder. 

EXPERIMENTS.  For  the  performance  of  the  experiments  on  acute 
toxic  gastritis,  cats  are  to  be  carefully  and  deeply  anaesthetized 
with  ether,  from  which  they  do  not  recover.  Three  animals  are 
given  respectively  carbolic  acid,  sulphuric  acid  and  nitric  acid 
through  a  glass  stomach  tube.  The  autopsy  is  performed  in  15 
minutes  and  the  stomachs  studied  grossly  and  histologically.  For 
the  production  of  gastric  ulcer,  two  erosion  experiments  are  per- 
formed. In  the  first,  6  guinea  pigs  are  given  about  o.ooi  gram 
snake  venom  and  the  autopsies  performed  at  the  end  of  48  hours, 
typical  haemorrhagic  erosions  appearing  in  several  of  the  animals. 
A  dog  is  anaesthetized  and  a  small  amount  of  agar  aseptically  in- 
jected beneath  the  mucosa  of  the  stomach.  Autopsy  at  the  end 
of  48  hours  shows  erosion  of  the  separated  mucosa.  Of  the  in- 
testinal lesions  the  most  instructive  appears  to  be  the  produc- 


PATHOLOGICAL  ANATOMY  OF  THE  ALIMENTARY  CANAL     371 

tion  of  intussusception.  This  is  done  under  ether  anaesthesia 
and  aseptically,  it  being  found  necessary  to  place  one  or  two 
stitches  so  as  to  maintain  the  intussusception.  Autopsy  at  the  end 
of  24  hours  shows  local  peritonitis,  gangrene  and  the  mode  of 
obstruction. 


371  c 


371  e 


THE  PATHOLOGY  OF  THE  PANCREAS 

The  pancreas  is  a  large  compound  gland  of  entodermal  origin, 
consisting  of  lobes  and  lobules,  and  resembling  in  its  general  struc- 
ture the  parotid  and  submaxillary  gland.  It  contains  enclosed 
within  it  an  epithelial  structure,  which  differs  anatomically  from 
that  of  the  acini,  has  no  connection  with  the  secretory  ducts,  its 
secretion  passing  directly  into  the  blood.  These  structures  are 
known  as  islands  of  Langerhans.  They  are  more  abundant  in  the 
tail  and  body  of  the  pancreas  than  in  the  head,  and  may  also  be 
found  in  the  fat  and  connective  tissue  surrounding  the  pancreas; 
their  secretion  is  believed  to  serve  an  important  part  in  sugar  metab- 
olism. The  relation  of  cells  and  vessels  resembles  that  of  the  liver, 
being  composed  of  bands  of  epithelial  cells  forming  a  framework 
between  which  run  blood  vessels  in  close  relation  with  the  cells. 
The  pancreas  has  no  capsule  and  contains  a  considerable  amount 
of  connective  tissue  distributed  around  the  ducts,  and  between  the 
lobules. 

The  organ  has  a  relatively  high  resistance  to  toxins  which  produces 
degenerations  in  other  organs.  The  parenchymatous  degenera- 
tions, so  common  in  the  infectious  diseases,  either  are  not  present 
or  in  but  slight  degree.  The  pancreas  is  also  resistant  to  infections, 
particularly  those  of  haematogenous  origin.  In  cases  of  haematog- 
enous  tuberculosis,  miliary  tubercles  rarely  are  found  in  its  tissue. 
In  congenital  syphilis  large  numbers  of  treponemata  may  be  found 
in  the  gland  with  but  few  lesions  associated  with  their  presence; 
the  lesions  of  acquired  syphilis  are  rare  also.  Metastatic  abscesses 
are  infrequent  and  the  same  is  true  of  primary  and  secondary 
tumors.  In  these  relations  the  pathology  of  the  pancreas  is  similar 
to  that  of  the  parotid  and  submaxillary  glands,  and  what  has  been 
said  of  the  pancreas  holds  true  for  these  glands  also.  Injurious  sub- 
stances affecting  the  gland  usually  reach  it  by  means  of  the  secretory 
ducts  and  the  pathology  of  the  pancreas  is  intimately  related  to  its 
ducts.  It  possesses  two  secretory  ducts;  the  chief  of  these  is  the 

372 


THE  PATHOLOGY  OF  THE  PANCREAS  373 

duct  of  Wirsung  which  begins  at  the  tail,  runs  through  the  middle  of 
the  pancreas,  bending  downward  as  it  passes  through  the  head. 
Branches  from  other  portions  of  the  pancreas  enter  into  this  duct  at 
right  angles.  It  descends  in  front  of  the  common  bile  duct  and 
empties  in  common  with  the  latter  into  the  duodenum  at  the  papilla 
of  Vater.  It  often  terminates  in  the  floor  of  the  papilla,  thus  giving 
a  common  opening  for  both  pancreatic  and  bile  ducts.  The  tribu- 
tary ducts  of  the  head  are  larger  than  the  others.  A  large  branch 
of  the  pancreatic  duct,  the  duct  of  Santorini  which  is  the  chief  duct 
of  the  head  of  the  pancreas,  may  empty  into  the  duct  of  Wirsung 
as  this  passes  through  the  head,  but  in  about  one-half  of  the  cases 
opens  independently  into  the  duodenum.  Even  when  so  terminat- 
ing, it  still  retains  its  connection  with  the  duct  of  Wirsung  and  the 
entire  secretion  of  the  gland  may  be  discharged  through  it.  The 
pancreatic  secretion  plays  an  important  part  in  digestion  by  means 
of  its  three  enzymes,  trypsin,  diastase  and  lipase.  It  is  generally 
believed  that  the  internal  secretion  produced  by  the  islands  of 
Langerhans  contains  the  enzyme  necessary  for  the  hydrolysis  or 
oxidation  of  sugar,  and  in  the  absence  of  this  secretion  sugar  accu- 
mulates in  the  blood  and  is  excreted  by  the  kidneys,  glycosuria. 
Regeneration  of  the  pancreas  takes  place  to  a  limited  extent  only. 

DEGENERATION  AND  NECROSIS.  Small  foci  of  necrotic  cells  not 
infrequently  are  found  in  the  pancreas.  These  vary  in  size  from 
single  necrotic  cells  to  areas  a  millimeter  or  more  in  diameter  and 
usually  occupy  no  fixed  location  within  the  lobule.  In  association 
with  the  necrosis,  there  is  infiltration  with  polynuclear  leucocytes. 
Small  foci  of  atrophy  and  increase  of  connective  tissue  are  found, 
which  represent  the  results  of  such  necroses. 

Atrophy  and  sclerosis  affecting  the  entire  organ  and  leading  to 
diminution  in  size  and  induration  also  may  occur.  The  surface  is 
uneven  and  irregular.  This  change  may  take  place  in  the  pancreas 
without  involving  the  islands  of  Langerhans  in  the  process,  or  these 
may  also  be  affected.  The  pancreas  may  also  be  affected  together 
with  the  liver  in  haemochromatosis.  In  this  condition  there  is 
atrophy  and  sclerosis  of  the  gland  associated  with  the  presence  of 
large  amounts  of  iron-containing  pigment  in  the  interstitial  tissue. 
When  the  Islands  of  Langerhans  are  involved,  diabetes  may  be  asso- 
ciated with  the  pigmentation,  the  conditionbeing  known  clinically 
as  bronze  diabetes. 


374  PATHOLOGY 

INFLAMMATIONS.  Three  types  of  acute  inflammation  of  the 
pancreas  are  described.  In  acute  hcemorrhagic  pancreatitis  the 
pancreas  is  enlarged  and  infiltrated  with  blood.  The  condition 
may  appear  in  foci,  or  the  entire  organ  may  present  the  appearance 
of  haemorrhagic  infarction.  The  blood  may  pass  from  the  pancreas 
into  the  surrounding  tissue  and  into  the  lesser  peritoneal  cavity. 
Microscopically,  the  gland  shows,  in  addition  to  the  haemorrhage, 
areas  of  necrosis  of  the  parenchyma  and  cellular  and  fibrinous 
exudation.  The  haemorrhagic  condition  may  be  associated  with 
gangrenous  pancreatitis  in  which  the  gland  is  enlarged,  soft  and 
friable,  the  color  varying  from  gray  to  black.  Complete  sequestra- 
tion of  the  necrotic  tissue  may  take  place  and  the  pancreas  be  repre- 
sented by  a  necrotic,  soft  gray  mass  lying  free  in  the  lesser  peritoneal 
cavity.  Suppuration,  in  the  form  either  of  circumscribed  abscesses 
or  as  a  purulent  infiltration  of  the  tissue,  is  comparatively  rare, 
but  may  be  combined  with  the  haemorrhagic  form.  The  origin  of 
acute  pancreatitis  has  been  cleared  up  by  experimental  study. 
It  has  been  found  that  the  injection  of  a  large  number  of  sub- 
stances into  the  pancreatic  duct  will  produce  the  condition.  The 
injection  of  bile  into  the  duct  produces  extensive  injury  and  in  man 
the  disease  often  follows  the  occlusion  of  the  papilla  by  a  gall  stone 
which  allows  the  bile  from  the  common  bile  duct  to  enter  the  pan- 
creatic duct;  this  takes  place  only  when  the  ducts  are  united  near 
the  opening.  Such  conditions  in  the  pancreas  frequently  are  ac- 
companied by  fat  necrosis.  This  is  due  to  an  escape  of  the  pan- 
creatic fluid  into  the  tissue,  leading  to  the  production  of  foci  of 
necrosis  in  the  interstitial  fat  of  the  gland,  or  in  the  surrounding  fat 
or  in  the  fat  of  the  peritoneal  cavity.  (See  necrosis,  page  43. ) 

Calculi  may  form  in  the  ducts,  producing  occlusion  followed  by 
cyst  formation.  There  is  usually  considerable  atrophy  of  the  tissue 
associated  with  this  condition. 

ACUTE  GANGRENOUS  PANCREATITIS 

Anatomical  Diagnoses.  Acute  gangrenous  pancreatitis;  Acute 
peritonitis;  Fat  necroses;  Chronic  cholecysitis;  Chronic  cholan- 
gitis;  Cholycystotomy;  Chronic  localized  peritonitis;  Jaundice; 
Ulcer  of  lower  lip;  Multiple  haemorrhages  in  lungs  and  skin; 
Chronic  perisplenitis;  Concretion  in  duct  of  Wirsung;  Subpial 
oedema;  Cyst  of  choroid. 


THE  PATHOLOGY  OF  THE  PANCREAS        375 

White,  male,  age  twenty-seven  years.  Body  well  developed,  fairly 
well  nourished.  Rigor  mortis  and  lividity  present.  Skin  is  yellow.  In 
lumbar  region  and  over  the  left  knee  are  areas  showing  discrete,  pete- 
chial  and  macular  purpuric  spots.  On  right  side  of  lower  lip  is  an 
ulcerated  area  1.5  cm.  in  diameter.  Slight  oedema  below  the  lower 
eyelids.  In  right  upper  quadrant  of  abdomen  opposite  attachment  of 
ninth  rib  and  extending  vertically  downward  for  6  cm.  is  an  operation 
wound  the  lower  half  of  which  is  healed;  the  upper  half  is  open  and  dis- 
charges a  brownish  colored  thick  material.  The  edges  of  the  wound  pale 
reddish  brown.  Two  small  sloughing  ulcers  on  either  side  of  the  wound 
at  site  of  skin  sutures.  Sclera  and  conjunctivae  markedly  jaundiced. 

Peritoneal  cavity.  Subcutaneous  fat  moderate  in  amount.  Irregu- 
larly distributed  over  the  peritoneum;  covering  the  great  omentum  and 
the  caecum,  are  numerous  small  discrete  irregularly  shaped  grayish-white 
to  yellowish-white,  soft,  rather  granular  areas.  They  average  from  3  to 
5  mm.  in  diameter.  Some  of  them  over  the  caecum  have  a  distinct  green- 
ish discoloration.  The  transverse  colon,  the  lesser  omentum  and  stomach 
bulge  forward  and  beneath  them  distinct  fluctuation  is  present.  This 
fluctuation  is  produced  by  the  contents  of  an  abscess  cavity  which  is 
situated  in  the  lesser  peritoneal  cavity.  This  cavity  contains  1500  c.c. 
of  a  brownish,  gruel-like  fluid  throughout  which  small  gray-white  bits 
of  tissue  are  seen.  Its  walls  are  shaggy  and  lined  with  a  gray,  necrotic 
material.  The  foramen  of  Winslow  is  obliterated  by  dense  adhesions. 
This  cavity  continues  along  the  lower  surface  of  the  left  lobe  of  the  liver 
to  a  slight  extent  under  the  right  lobe,  and  downward  behind  the  peri- 
toneum along  the  course  of  the  descending  colon  as  far  as  the  caecum. 
This  cavity  communicates  with  the  gall  bladder  by  an  opening  in  this 
and  through  the  gall  bladder  with  the  opening  in  the  abdominal  wall. 

Pleural  cavities  normal. 

Pericardial  cavity  normal. 

Heart.  Weight  280  grams.  Myocardium  normal.  Cusps  of  aortic 
valve  slightly  thickened  at  bases.  There  are  a  few  yellowish- white, 
thickened  areas  in  the  aortic  segment  of  the  mitral  valve.  Coronaries 
normal. 

Lungs.  Both  are  crepitant  throughout.  On  section  a  few  small, 
dark  reddish  areas  are  irregularly  distributed. 

Spleen.  Weight  132  grams.  Soft.  Covered  with  dense  fibrous 
adhesions.  Near  the  hilus  is  a  dark  green  soft  area.  Spleen  generally 
deep  red.  Trabeculae  prominent. 

Gastro-intestinal  tract.  (Esophagus  negative.  Stomach  con- 
tracted and  empty.  Rugae  prominent.  No  gastric  ulceration.  Walls 
rather  soft,  greenish  gray  and  covered  with  fibrous  tags.  Duodenum 


376  PATHOLOGY 

deep  greenish  gray.  Biliary  and  pancreatic  ducts  are  patent,  but  small. 
Intestines  normal,  except  for  adhesions  about  the  caecum  and  transverse 
colon.  Intestinal  contents  are  grayish  white  and  contain  small,  "  chalky- 
like"  flakes  scattered  throughout.  Examination  shows  large  amount 
of  fat. 

Pancreas.  Practically  the  whole  of  the  pancreas  is  represented  by  a 
grey  or  white  to  deep  red,  soft,  friable,  soapy  feeling  material.  A  small 
portion  of  the  head  remains  as  a  deep  red  rather  firm  tissue.  The  duct 
of  Wirsung  about  i  cm.  from  its  opening  into  duodenum  is  occluded  by 
a  gray,  firm  mass,  3  mm.  in  diameter. 

Liver.  Slightly  increased  in  size,  deeply  bile  stained,  lobules  distinct. 
Portal  systems  dilated.  Gall  bladder  is  continuous  with  the  fistulous 
opening  in  the  abdomen.  Cystic  duct  is  somewhat  narrowed;  it  is 
impossible  to  pass  a  probe  through  it  in  either  direction.  The  hepatic 
duct  patent,  as  is  also  the  common  bile  duct,  though  narrowed  just 
prior  to  the  opening  into  the  duodenum.  No  gall  stones. 

Kidneys.  Weight  350  grams.  Capsules  not  adherent  and  leave  a 
smooth  surface  on  stripping.  On  section  the  cut  edges  of  the  kidney 
slightly  everted.  Cortex  0.75  to  i  cm.  in  thickness.  Deep  red.  Glom- 
eruli  indistinct.  Pyramids,  pelvis  and  ureters  normal. 

Bladder.  Contains  about  150  c.c.  of  clear,  straw-colored  urine. 
Genital  organs  normal. 

Aorta  rather  pale. 

Head.  Brain,  weight,  1370  grams.  Scalp  covered  with  short  black 
hair.  Scalp  and  calvarium  normal.  There  is  slight  oedema  of  the  pia 
and  a  slightly  increased  amount  of  cerebrospinal  fluid  at  the  base  of 
the  brain.  The  fluid  in  the  lateral  ventricles  is  normal  in  amount  and 
bile  stained.  There  is  a  small  cyst  in  the  choroid  plexus  of  the  left 
lateral  ventricle.  The  cerebrum,  cerebellum,  pons,  medulla  and  basal 
nuclei,  on  serial  section,  are  normal. 

Middle  ears  normal. 

REMARKS.  The  haemorrhages  in  the  skin  and  elsewhere  are 
related  to  the  jaundice.  The  bile  salts  favor  haemorrhage  by  retard- 
ing the  coagulation  time  of  the  blood  and  probably  also  by  produc- 
ing endothelial  necroses.  The  acute  gangrenous  pancreatitis  is 
interesting  in  association  with  the  calculus  in  the  duct  of  Wirsung. 
Had  there  been  a  single  opening  through  which  the  two  ducts 
discharge,  and  had  the  calculus  occluded  this,  the  acute  pancreatitis 
would  be  easy  of  explanation  by  the  entry  of  bile  into  the  pan- 
creatic duct.  In  this  case  the  obstruction  of  the  duct  by  the  cal- 
culus facilitated  the  infection  of  the  contents  producing  acute 


THE  PATHOLOGY  OF  THE  PANCREAS       377 

inflammation.  The  fat  necroses  are  due  to  escape  of  pancreatic 
secretion  into  the  tissue  and  the  white  fatty  contents  of  the  intestine 
to  the  absence  of  the  action  of  the  pancreatic  secretion. 

EXPERIMENTS.  Acute  haemorrhagic  and  necrotic  pancreatitis  is 
produced  by  injecting  into  the  pancreatic  duct  of  a  dog  (ether  an- 
aesthesia), either  through  the  papilla  or  directly  into  the  duct,  about 

3  c.c.  dog's  bile  (same  animal  —  obtained  by  gall  bladder  puncture) . 
At  the  end  of  24  hours  most  marked  pancreatitis  and  extensive  fat 
necrosis  appear.    Most  important  in  connection  with  the  pancreas 
is  diabetes  and  at  this  time  experiments  in  glycosuria  are  best  made. 
Pancreatic  glycosuria  is  produced  by  completely  extirpating  the 
dog's   pancreas,    aseptically   and   under   ether   anaesthesia.    The 
animal  is  observed  in  a  metabolism  cage.    For  other  forms  of 
glycosuria  the  rabbit  is  used  as  follows:   for  renal  glycosuria,  the 
hypodermic  injection  of  0.25  gram  phlorrhizin  dissolved  in  5.0  c.c. 
warm  water;  for  asphyxial  glycosuria,  hypodermic  injection  2-3  c.c. 

4  per  cent  morphine  sulphate  solution;  adrenalin  glycosuria,  hypo- 
dermic injection  2.0  c.c.  i:  1000  adrenalin  solution.     The  animals 
are  observed  closely  in  metabolism  cages  and  advantage  is  taken 
of   the  morphinized  animal    to  make  pneumographic  tracings  of 
Cheyne-Stokes  respiration.    The  so-called  puncture  glycosuria  is 
produced  as  follows:   Under  ether  anaesthesia  expose  the  occipital 
protuberance  of  a  rabbit's  skull,  trephine  just  posteriorly  and  push 
in  through  the  cerebellum  a  special  puncture  knife.    Hold  the  in- 
strument so  that  it  will  bisect  the  line  joining  the  external  opening 
of  the  two  ears  and  send  it  in  until  it  is  felt  to  have  met  the  basilar 
bone.    Place  in  metabolism  cage  and  examine  the  urine  in  2  hours. 
At  death  perform  autopsy  and  verify  position  of  puncture. 


377 


377  b 


377 


377  d 


THE  PATHOLOGY  OF  THE  LIVER 

THE  INFECTIONS  of  the  liver  present  no  peculiarities  except  those 
due  to  anatomical  structure  and  which  determine  the  mode  of 
entry  of  infecting  organisms  and  their  extension.  The  abundant 
blood  supply  of  the  liver  and  the  slowness  of  circulation  favor  the 
entry  of  organisms  from  the  blood  and  the  comparative  infrequency 
of  infection  argues  a  relatively  high  degree  of  resistance. 

DEGENERATION  AND  REGENERATION.  The  key  to  most  of  the 
anatomical  lesions  of  the  liver  is  given  by  a  consideration  of  the 
relations  between  degeneration  and  regeneration  and  repair.  Both 
the  less  severe  forms  of  degeneration  and  necrosis  are  common  in 
the  liver.  The  liver  cells  are  extremely  sensitive  to  the  action 
of  toxins,  bacterial  or  other,  which  are  formed  in  the  course  of 
infections  and  to  the  toxic  action  of  certain  drugs,  such  as  phosphor- 
ous and  chloroform.  In  most  cases  the  cells  around  the  centres 
of  lobules  are  more  easily  affected  and  the  necroses  are  more  usually 
central.  In  other  cases  the  necrosis  may  be  confined  to  the  mid- 
zone  of  the  lobule  and  rarely  to  the  periphery.  In  phosphorous 
poisoning  the  necrosis  is  irregular  in  its  distribution  and  in  yellow 
fever  single  cells,  chiefly  in  the  periphery  of  the  lobule,  are  affected. 
Extensive  necrosis  follows  fracture  of  the  liver  due  to  trauma,  the 
fracture  shutting  off  areas  from  circulation.  The  process  of 
regeneration  and  repair  has  already  been  considered  (see  page  128). 

ACUTE  YELLOW  ATROPHY.  The  most  extreme  degrees  of  degen- 
eration and  necrosis  are  found  in  acute  yellow  atrophy  of  the  liver.  In 
the  most  acute  cases  of  this  disease,  the  liver  is  small;  in  the  adult 
the  weight  may  be  reduced  to  600  grams,  lax  in  consistency,  the 
edges  sharp,  the  color  yellow  or  yellow  brown.  The  laxity  of  tissue 
is  so  great  that  the  organ  flattens  when  laid  on  a  surface.  Micro- 
scopically, the  picture  is  that  of  intense  degeneration  with  much 
fat  in  the  cells,  necrosis  and  histolysis.  In  places  the  liver  cells 
are  represented  by  a  granular  mass  in  which  neither  cell  outlines 
nor  nuclei  can  be  found.  Large  areas  of  the  liver  are  so  affected, 
but  in  places  comparatively  well  preserved  lobules  may  be  found. 
The  condition  where  the  acute  degeneration  is  most  marked  is  such 

378 


THE  PATHOLOGY  OF  THE  LIVER 


379 


as  might  be  produced  by  washing  out  most  of  the  liver  cells  leaving 
the  collapsed  framework.     In  the  less  acute  cases  the  atrophy  is 
marked,  but  the  loss  of  consistency  not  so  extreme  and  sections  of 
the  Kver  shows  an  alternation  of  slightly  elevated  irregularly  dis- 
tributed yellow  areas  in  a  tough,  lax,  red  or  red-brown  tissue.    The 
yellow  areas  have  irregular  contours  and  may  be  several  centimeters 
in  diameter.    Microscopic  examination  at  this  stage  shows  in  the 
red  tissue  a  network  of  fine  canals  lined  with  low  epithelium.    A 
lumen  sometimes  is  visible.    Between  these  structures  is  a  tissue 
filled  with  large  cells  of  endothelial  character  and  abundant  capil- 
laries.    In  places  areas  of  injected  capillaries  are  found  which  in 
arrangement  simulate  those  of  the  lobule.    In  the  yellow  areas  liver 
tissue  variously  altered  is  found.    At  the  edges  of  the  yellow  areas, 
degenerated  and  necrotic  cells  are  found  and  there  is  everywhere  a 
varying  degree  of  degeneration.    In  places  the  degenerated  areas 
show  the  normal  architecture  of  the  liver,  in  others  there  is  a  wide 
departure  from  this,  shown  in  the  increased  size  and  irregular 
structure  of  the  lobules.    The  liver  cells  are  large,  the  bile  capil- 
laries dilated  and  often  filled  with  bile  casts.    Fragments  of  such 
casts  may  be  seen  within  endothelial  cells  in  the  sinuses  and  the 
casts  themselves  may  project  from  the  bile  capillaries  into  the 
sinuses.    In  the  red  areas  the  interlobular  spaces  are  represented 
by  the  bile  ducts  which  are  but  little  altered;    the  interlobular 
vessels  are  not  so  apparent.     Cases  have  been  described  of  apparent 
recovery  in  which  the  liver  returns  to  a  normal  color  and  consists 
of  irregular  masses  of  liver  tissue  in  which  the  lobules  are  large  and 
irregular  in  structure,  the  masses  surrounded  by  and  infiltrated 
with  dense  connective  tissue  containing  the  duct-like  structures 
already  described.    The  disease  ordinarily  runs  an  acute  course, 
with  jaundice  and  delirium,  death  taking  place  within  two  or  three 
weeks.    The  aetiology  is  obscure;  the  condition  often  accompanies 
or  follows  severe  infections,  may  follow  pregnancy,  prolonged  chloro- 
form narcosis,  or  appear  without  any  recognized  antecedent  condi- 
tion.    The  condition  is  obviously  one  of  degeneration  and  histolysis 
of  the  liver  parenchyma  followed  by  regeneration,  most  of  the 
liver  tissue  in  the  subacute  and  chronic  cases  being  regenerated. 
There  has  been  considerable  dispute  as  to  the  character  of  the  duct- 
like  structures  in  the  atrophic  tissue.    They  form  an  anastomosing 
network  in  this,  which  communicates  with  the  remaining  inter- 


380  PATHOLOGY 

lobular  bile  ducts,  and  they  are  due  to  regenerative  outgrowth  from 
the  original  bile  ducts.  Structures  very  similar  in  character  may 
be  produced  by  atrophy  of  the  liver  cell  columns,  but  in  acute 
yellow  atrophy  there  is  necrosis  and  histolysis  of  the  liver  tissue  and 
not  a  simple  atrophy.  The  capacity  of  the  bile  ducts  epithelium 
for  regenerative  proliferation  is  shown  in  the  regeneration  of  liver 
following  traumatic  destruction  (see  page  128). 

CIRRHOSIS  OF  THE  LIVER.  (Chronic  interstitial  hepatitis.}  The 
essential  conditions  in  cirrhosis  are  degeneration  and  destruction 
of  tissue  followed  by  connective  tissue  increase  and  new  formation 
of  parenchyma.  Instead  of  being  acute,  as  in  yellow  atrophy,  the 
process  is  extremely  chronic  extending  over  years,  and  there  is  great 
variety  in  the  anatomical  picture,  due  to  the  period  of  disease, 
rapidity  of  progress,  character  of  degeneration  and  extent  of  repair. 
The  most  common  and  most  characteristic  form  of  the  disease  is 
atrophic  cirrhosis.  In  this  the  liver  is  reduced  in  size,  weights  under 
1000  grams  in  adults  are  not  uncommon,  it  is  firm  and  the  surface 
irregular  and  nodular,  hobnail  liver.  The  irregular  and  nodular 
surface  is  due  to  projections  of  the  less  altered  parenchyma  sepa- 
rated by  cicatricial  depressions.  The  color  varies;  it  may  be  darker 
than  normal,  yellow  or  pale  from  an  increased  fat  content,  or  green 
or  green  yellow  from  retained  bile  pigment.  On  section  it  is  dense, 
often  of  almost  cartilaginous  consistency,  and  the  cut  surface  shows 
nodules  separated  by  more  transparent  bands  of  connective  tissue. 
Microscopically,  the  picture  corresponds  with  the  macroscopic  ap- 
pearance. The  connective  tissue  bands  separate  the  areas  of  paren- 
chyma. Single  (monolobular  cirrhosis)  or  several  (multilobular 
cirrhosis)  lobules  may  be  so  enclosed,  and  the  connective  tissue  often 
extends  hi  finer  bands  into  the  lobule.  The  bands  form  around 
the  periphery  of  the  lobules,  there  being  no  increase  of  tissue  around 
the  central  vein  (cardiac  cirrhosis,  see  page  90).  There  is  always 
infiltration  of  the  connective  tissue  with  lymphoid  cells  which  often 
are  aggregated  hi  clusters.  The  connective  tissue  is  fibrillar  and 
contains  a  large  amount  of  elastic  tissue.  The  duct-like  structures, 
previously  described,  are  almost  always  present.  At  the  edge  of 
the  liver  cells  they  are  continuous  with  evidently  atrophic  cells, 
and  these  again  are  continuous  with  normal  cells  and  the  formation 
of  duct-like  structures  by  atrophy  of  liver  cells  in  the  usual  mode. 
The  arteries  of  the  liver  rarely  show  lesions  even  in  cases  of  arterio- 


THE  PATHOLOGY  OF  THE  LIVER  381 

sclerosis  elsewhere;  the  visible  portal  veins  are  usually  dilated. 
Small  masses  of  liver  cells  without  lobular  arrangement  may  be 
enclosed  in  the  connective  tissue.  The  liver  cells  in  form  and  in 
arrangement  show  no  considerable  departure  from  normal;  fre- 
quently areas  evidently  of  new  formation,  are  found  in  which  the 
lobules  are  much  larger  than  normal  and  the  hepatic  vein  eccentri- 
cally placed.  The  newly  formed  cells  are  often  larger,  more  distinct 
and  the  nuclei  contain  more  chromatin  than  the  normal.  In  other 
cases  various  evidences  of  degeneration,  and  even  extensive  cell 
necrosis,  is  seen.  A  peculiar  form  of  degeneration  characterized 
by  amitotic  nuclear  division,  the  single  cell  containing  a  number  of 
nuclei  with  but  small  chromatin  content,  is  not  infrequent.  The 
presence  or  abscence  of  cell  degeneration  is  due  to  the  examination 
being  made  hi  periods  of  extension  or  quiescence  of  the  disease. 
The  disease  is  essentially  one  of  adults;  it  is  due  to  the  long  con- 
tinued action  of  toxic  agents  of  little  intensity  of  action,  and  fre- 
quently is  associated  with  alcoholism.  It  is  not  so  infrequent  in 
children  as  generally  is  supposed.  Arterio-sclerosis,  which  plays 
so  important  a  part  in  the  very  similar  condition  of  chronic  diffuse 
nephropathy,  seems  to  be  in  so  far  as  local  arterio-sclerosis  is  con- 
cerned, of  no  aetiological  significance  in  atrophic  cirrhosis. 

The  underlying  conditions  in  hypertrophic  cirrhosis  (Hanoi's 
cirrhosis)  are  very  similar  to  those  of  the  atrophic,  but  the  lesions 
differ  both  in  their  macroscopic  and  microscopic  aspects.  In  this 
condition  the  liver  is  greatly  enlarged,  the  weight  in  adults  fre- 
quently being  3000  grams,  the  surface  either  smooth  or  finely  granu- 
lar, the  color  pale  or  yellow.  The  consistency  is  greatly  increased 
and  the  surface  homogeneous  on  section.  Microscopically,  there 
usually  is  well-marked  degeneration  and  a  diffuse  formation  of 
connective  tissue  not  only  around  the  periphery  of  the  lobules,  but 
extending  into  them  and  around  individual  cells.  In  the  connective 
tissue  there  are  large  numbers  of  ducts  and  marked  lymphoid  cell 
infiltration.  There  is  degeneration,  necrosis  and  destruction  of 
liver  cells.  The  condition  clinically  is  always  more  acute  than  is 
the  atrophic  form.  It  is  a  comparatively  rare  disease.  Hanot's 
cirrhosis  has  been  described  by  French  authors  as  probably  due 
to  an  indefinite  but  specific  infection,  and  there  is  little  doubt  that 
infectious  processes  play  an  important  rdle  in  the  production  of 
all  forms  of  cirrhosis. 


382  PATHOLOGY 

Various  other  types  of  cirrhosis  are  distinguished,  as  biliary, 
syphilitic,  etc.,  and  which  are  due  to  different  modes  of  production 
of  the  primary  injury. 


A  CASE  OF  ACUTE  YELLOW  ATROPHY  OF  THE  LIVER 

Anatomical  Diagnoses.  Acute  yellow  atrophy  of  the  liver;  Hypo- 
static  congestion  of  the  lungs;  Acute  congestion  of  the  spleen; 
Localized  congestion  of  small  intestines;  General  bile  pigmenta- 
tion of  the  tissues. 

White,  male,  age  forty  years.  Admitted  to  hospital  January  twenty- 
nine,  with  the  following  history:  For  three  weeks  had  not  been  feeling 
well.  One  week  before  admission  quit  work  on  account  of  general  weak- 
ness and  because  he  was  becoming  yellow.  Three  days  before  he  came 
to  hospital  became  delirious.  On  admission  to  hospital  was  wildly 
delirious  requiring  restraint.  Pulse  was  not  rapid.  Passed  urine  and 
f eces  involuntarily.  Physical  examination  was  negative  except  for  the 
jaundice  and  for  a  marked  decrease  in  hepatic  dullness  which  was  re- 
duced in  the  right  nipple  line  to  an  area  not  more  than  one  inch  in  width. 
Diagnosis  of  acute  yellow  atrophy  of  liver.  During  the  next  twenty- 
four  hours  the  patient  became  quieter,  but  was  not  able  mentally  to 
give  any  account  of  himself.  He  died  before  midnight  January  3ist. 

Body  powerfully  built,  fairly  well  nourished,  not  fat.  The  entire 
surface  of  the  body  and  conjunctivas  intensely  jaundiced.  The  jaundice 
is  a  pale  yellow  color  except  along  the  inner  surfaces  of  the  thighs  and 
about  the  pubes,  where  the  yellow  has  deepened.  The  dependent  parts 
show  post-mortem  lividity,  with  a  combination  of  purple-red  and  yellow 
areas.  Scattered  over  the  thorax  there  are  small  red  naevi  from  2  to 
5  mm.  in  diameter,  from  ten  to  fifteen  in  number,  and  some  of  these  are 
capped  by  a  small  superficial  crust.  There  are  no  areas  of  haemorrhage 
in  the  skin.  Rigor  mortis  marked. 

The  abdomen  is  moderately  distended,  tympanitic.  Percussion  of  the 
right  thorax  shows  anteriorly  pulmonary  resonance,  passing  directly 
into  the  abdominal  tympany  without  any  intervening  area  of  hepatic 
flatness.  On  opening  the  abdomen  the  intestines  are  moderately  dis- 
tended; liver  or  spleen  not  visible.  The  peritoneum  is  everywhere 
glistening  and  smooth.  There  is  no  increase  in  peritoneal  fluid.  The 
small  intestine  is  moderately  distended  with  gas,  the  large  intestine, 
except  the  caecum,  is  rather  collapsed.  The  lower  border  of  the  liver 
is  well  above  the  costal  margin  and  has  to  be  pulled  down  in  order  to 
be  visible.  The  lower  border  of  the  spleen  is  slightly  above  the  costal 


THE  PATHOLOGY  OF  THE  LIVER  383 

margin.  The  thorax  and  both  pleural  cavities  are  free  from  fluid  and 
adhesions. 

The  lungs  are  rather  voluminous,  deeply  pigmented  with  carbon  in 
the  posterior  portions;  and  the  lower  lobes  are  soggy  and  firmer  than 
the  tissue  elsewhere.  The  lung,  however,  crepitates  everywhere.  Cut 
surface  of  the  lungs  is  moist.  A  moderate  amount  of  mucous  or  muco- 
pus  exudes  from  the  small  bronchi  and  from  the  alveoli,  and  a  frothy 
serum  in  moderate  amount  runs  out.  There  are  no  distinct  areas  of 
consolidation.  The  entire  cut  surfaces  are  a  fairly  uniform  dark  reddish 
color. 

The  peribronchial  lymph  nodes  are  very  slightly  enlarged,  show  car- 
bon pigmentation,  but  no  other  abnormality.  The  bronchi  are  con- 
gested and  contain  a  moderate  amount  of  mucous  and  muco-pus.  The 
pericardium  contains  about  75  c.c.  of  clear  fluid  of  a  dark  yellow  color. 
The  pericardium  is  everywhere  smooth  and  glistening.  The  heart  is 
normal  in  size  and  shape.  Endocardium  normal;  valves  normal; 
coronary  arteries  normal.  The  endothelial  surfaces  of  the  aorta  and 
pulmonary  artery  are  stained  yellow  by  the  bile  pigmentation,  as  is 
also  the  fat  and  areolar  tissue  about  the  heart. 

Liver.  Weight  1000  grams.  The  surface  of  right  lobe  shows  along  the 
upper  surface  two  rather  distinct  rounded  elevations  from  4  to  6  cm.  in 
diameter,  which  project  somewhat  above  the  surrounding  surface,  are 
dome-shaped,  the  contour  not  particularly  smooth,  there  being  small 
elevations  upon  the  general  rounded  surface.  The  lower  half  of  the 
right  lobe  shows  a  somewhat  elevated  surface  presenting  the  same  slight 
irregularity.  On  the  inferior  surface  this  same  arrangement  appears, 
and  on  the  inferior  surface  of  the  extreme  lower  portion  there  is  a  cleft 
in  the  surface  of  the  liver  4  cm.  long  and  3  cm.  deep.  As  seen  through 
the  capsule,  which  is  in  no  place  thickened,  these  more  elevated  areas 
are  yellow  or  yellow  red  in  color.  After  exposure  to  the  air  the  yellow 
becomes  green;  corresponding  to  the  smaller  elevations  on  the  surface 
of  the  larger  elevations,  there  is  a  slight  mottling,  the  more  elevated 
areas  being  more  yellow  and  the  depressed  areas  being  more  red.  Be- 
tween these  more  distinct  elevations  the  surface  of  the  liver  is  in  general 
red  and  slightly  wrinkled.  The  elevated  areas  are  firm,  the  larger  one 
distinctly  firmer  than  normal.  The  more  depressed  portions,  which  are 
red,  are  distinctly  flabby.  The  cut  surface  of  the  liver  shows  two  very 
distinct  appearances.  There  are  considerable  areas  which  are  red  in 
color,  showing  over  their  surface  a  fine  distribution  of  red-gray  tracery 
of  somewhat  the  appearance  that  is  given  by  the  liver  of  chronic  passive 
congestion  without  the  central  depressions.  The  other  parts  of  the  liver 
are  bright  yellow,  turning  green  on  exposure  to  the  air,  and  these  areas 


384  PATHOLOGY 

seem  to  be  made  up  of  liver  lobules  distinctly  larger  than  those  sug- 
gested by  the  tracery  in  the  red.  It  would  seem  as  if  there  were  a  small 
central  vein  and  about  it  liver  tissue  from  i  to  1.5  mm.  in  thickness, 
such  a  group  forming  what  is  taken  to  be  a  liver  lobule  somewhat  larger 
than  normal.  The  amount  of  these  two  different  kinds  of  tissue  varies 
on  a  given  cross  section.  In  portions  of  the  liver  they  are  equal,  in 
other  parts  red  predominates,  in  still  others  yellow.  The  vessels  seen 
on  the  section  appear  to  be  normal.  This  description  applies  entirely 
to  the  right  lobe  of  the  liver.  The  left  lobe  of  the  liver  is  represented 
by  a  thin,  flabby  red  tissue,  with  slightly  wrinkled  surface,  showing  at 
two  places  slightly  elevated  yellow  areas,  one  being  2  cm.  in  diameter, 
the  other  1.5  cm.  The  tissue  in  the  left  lobe  resembles  on  section  the 
red  parts  of  the  right  lobe,  and  is  distinctly  tougher  than  normal. 

The  spleen  weighs  205  grams,  is  somewhat  softer  than  normal.  Cut 
surface  is  of  uniform  dark  red  color  with  malpighian  bodies  just  visible; 
pulp  scrapes  away  slightly  more  easily  than  normal. 

Gastrointestinal  tract.  (Esophagus  is  normal.  The  stomach  is  con- 
siderably dilated  and  filled  with  a  brown-gray  fluid  containing  a  consider- 
able amount  of  mucous.  Mucous  membrane  of  the  stomach  is  normal 
except  for  a  considerable  amount  of  adherent  mucous.  Pyloric  ring 
is  contracted,  but  there  is  no  evident  hypertrophy  and  no  actual  obstruc- 
tion. The  small  intestine  is  normal,  except  for  a  distance  of  about 
eighteen  inches,  beginning  at  a  point  about  thirty-six  inches  above  the 
ileo-caecal  valve,  where  it  is  very  much  congested.  The  mucous  mem- 
brane is  dark  red  in  color.  In  places  this  congestion  is  uniform  in  its 
distribution,  in  other  places  it  affects  mainly  the  tops  of  the  folds  of  the 
mucous  membrane.  There  is  no  evidence  of  ulceration  or  erosion  in  this 
region  and,  except  for  this  area,  the  small  intestine  shows  no  other  ab- 
normality. Then  in  the  lower  portion  there  are  scattered  solitary 
follicles  showing  a  distinct  zone  of  hyperaemia  about  them.  The  large 
intestine  and  the  appendix  are  normal.  The  pancreas  is  large,  fairly 
firm  and  shows  no  abnormality  on  section.  The  biliary  ducts  and 
pancreatic  ducts  are  normal.  The  gall  bladder  is  filled  with  thick,  dark 
bile,  but  there  are  no  concretions  and  its  mucous  membrane  appears 
normal. 

The  kidneys  are  somewhat  larger  than  normal,  appear  slightly  swollen 
and  are  of  a  red-purple  color.  The  capsule  strips  quite  easily  from  the 
smooth  surface.  The  cut  surface  shows  a  rather  dark  tissue,  in  general 
color  purple  with  slightly  evident  yellowish  tint.  There  is  nothing 
abnormal  in  the  appearance  of  the  cortex  or  the  pyramids.  The  adrenals 
are  normal  in  appearance.  The  bladder,  prostate  and  testes  are  normal. 
The  aorta  is  normal.  The  thyroid  is  normal.  Some  of  the  lymph  nodes 


THE  PATHOLOGY  OF  THE  LIVER  385 

of  the  abdomen  are  moderately  enlarged  and  show  distinct  bile  pig- 
mentation. 

Microscopical  examination  of  the  liver.    Sections  of  liver  stained  in 
methylene  blue  and  eosin  show  two  distinct  areas;  in  one  of  these  areas, 
which  corresponds  with  the  red  areas,  the  liver  cells  have  disappeared 
leaving  foci  of  injection  and  haemorrhage  around  the  central  veins  and 
containing  great  numbers  of  epithelial  strands  or  ducts  around  the  portal 
vessels;  in  the  other,  which  corresponds  with  the  yellow  areas,  the  liver 
tissue  is  of  somewhat  atypical  character  with  increase  of  connective 
tissue.    More  detailed  examination  shows  in  the  red  areas  a  general 
collapse  of  the  tissue  with  diminution  of  the  distance  between  hepatic 
and  portal  vessels.    There  is  blood  both  free  and  in  spaces  which  corre- 
sponds with  liver  capillaries  between  which  is  thick  connective  tissue 
containing  numbers  of  cells.    There  is  great  thickening  of  the  tissue 
about  the  central  veins,  and  the  congestion  and  haemorrhage  are  most 
marked  about  the  central  veins.    In  the  portal  territories  the  artery, 
vein  and  bile  duct  appear  as  normally,  and  about  them  is  the  irregular 
network  of  epithelial  tubules.    The  strands  of  these  vary  in  diameter 
from  10  to  30  n.    The  outline  of  the  individual  cells  composing  them 
cannot  be  distinguished;   the  cells  appear  as  a  syncytium  containing  a 
large  number  of  nuclei  which  have  epithelial  characteristics.    Here  and 
there  definite  lumina  can  be  distinguished  in  the  structures.    This  net- 
work communicates  with  the  definite  bile  ducts  in  the  portal  spaces  but 
the  communications  are  rare.    The  bile  duct  gives  off  a  lateral  which 
at  first  has  the  characteristics  of  a  bile  duct,  but  quickly  takes  the 
character  of  the  network  and  forms  part  of  this.    The  network  is  closer 
near  the  portal  spaces.    Neither  nuclear  figures  nor  nuclei  indicating 
direct  division  are  found  in  the  network.    Pointed  processes  not  unlike 
forming  vessels  are  given  off  from  it.    In  places  there  is  a  change  in  the 
character  of  the  cells  composing  it.    The  cells  become  larger  and  fewer 
in  number,  the  nuclei  larger,  their  cytoplasm  acidophilic  and  there  are 
transitions  between  such  cells  and  definite  liver  cells.    Where  this  change 
is  taking  place,  there  are  numbers  of  polynuclear  and  large  endothelial 
cells  in  the  tissue.    Masses  of  liver  cells  are  connected  with  these  epithe- 
lial structures.    The  cells  show  no  evidences  of  degeneration,  they  are 
very  granular  and  have  large  nuclei  rich  in  chromatin.    The  capillary 
bile  ducts  between  the  cells  are  very  evident,  are  dilated  and  often  con- 
tain bile  casts.    The  interpretation  is  total  destruction  of  liver  tissue  and 
a  new  formation  by  development  of  the  epithelium  of  the  ducts  which 
represent  an  outgrowth  from  the  bile  ducts  into  liver  cells. 

The  yellow  areas  show  islands  of  liver  tissue  separated  by  bands  of 
connective  tissue.    These  islands  vary  in  size,  none  of  them  larger  than 


386  PATHOLOG\ 

i  mm.  The  lines  of  connective  tissue  have  an  indefinite  arrangement 
following  both  the  hepatic  and  portal  spaces.  The  liver  tissue  around 
the  central  veins  has  greatly  dilated  bile  capillaries  filled  with  casts  which 
occasionally  project  from  the  liver  cell  columns  into  the  capillaries. 
Such  casts  never  are  found  in  the  vicinity  of  the  portal  spaces.  About 
the  central  veins  also,  cells  in  various  stages  of  degeneration  are  found. 
Some  of  these  are  represented  by  vacuolated  masses,  others  by  irregular 
masses  of  cytoplasm  filled  with  bile  pigment,  and  in  their  vicinity  there 
are  numbers  of  phagocytic  endothelial  cells.  These  degenerated  cells 
in  part  occur  singly;  in  part  they  are  in  masses  which  are  continuous 
with  the  more  nearly  normal  cells.  It  is  difficult  to  determine  whether 
these  degenerated  cells  should  be  regarded  as  old  liver  cells  or  as  new 
cells  which  have  undergone  degeneration.  The  masses  of  liver  here  are 
atypical.  The  capillaries  are  in  places  short,  in  places  of  abnormal 
length,  and  the  trabeculae  of  the  liver  cells  in  places  conform  to  the  normal 
type  and  in  places  they  are  much  broader  making  four  or  five  rows  of 
cells.  About  the  portal  spaces  there  are  numbers  of  bile  ducts  both 
normal  and  atypical.  The  cells  are  intensely  granular  and  rather  smaller 
than  normal  cells.  The  capillaries  in  the  areas  contain  but  little  blood. 
The  interpretation  is  that  the  liver  tissue  in  the  yellow  areas  is  newly 
formed. 

REMARKS.  This  is  a  typical  case  of  acute  yellow  atrophy  of  the 
liver.  The  duration  cannot  be  determined  with  definiteness,  but 
the  acute  symptoms  are  of  but  nine  days'  duration.  It  is  almost 
impossible  to  avoid  the  conclusion  that  practically  the  entire  liver 
was  destroyed  and  that  the  yellow  areas  represent  regenerated  tissue. 

It  is  not  impossible  that  in  these  areas  the  destruction  was  slower 
and  that  much  of  the  regeneration  was  by  means  of  hyperplasia  of 
the  liver  cells.  The  jaundice  is  easily  understood.  Bile  was 
formed  in  the  cells,  but  the  tissue  was  so  altered  that  it  could  not 
easily  enter  the  bile  ducts;  it  accumulated  and  became  thickened 
into  casts  which  passed  from  the  bile  capillaries  directly  into  the 
blood. 

A  CASE  or  CIRRHOSIS  or  LIVER 

Anatomical  Diagnoses.  Cirrhosis  of  liver;  General  arterio-sclero- 
sis;  Chronic  peritonitis  (adhesive);  Chronic  pleurisy  (adhesive); 
Heart  hypertrophy;  Chronic  perisplenitis  (adhesive);  Ascites; 
Chronic  passive  congestion  of  spleen;  Chronic  passive  congestion 
of  kidneys;  Chronic  diffuse  nephropathy;  (Edema  of  lungs; 
(Edema;  Jaundice. 


THE  PATHOLOGY  OF  THE  LIVER  387 

White,  male,  age  sixty-one  years.  Body  well  developed  and  fairly  well 
nourished.  Post-mortem  lividity  is  marked  over  face  and  dependent 
portions  of  body.  Rigor  mortis  is  present.  There  is  oedema  of  ankles 
and  of  scrotum.  Sclerae  have  a  distinct  yellow  tinge.  The  abdomen 
makes  a  rather  abrupt  rise  just  below  the  ribs,  reaching  to  a  height  of 
30  cm.  above  the  table.  The  umbilicus  protrudes  and  the  contents  of 
the  abdomen  are  fluctuant.  The  skin  all  over  the  body  has  a  distinct 
yellow-green  color. 

Peritoneal  cavity.  Contains  about  11,000  c.c.  of  fluid  (9500  c.c. 
measured,  and  remainder  estimated).  This  fluid  has  a  distinct  red  tinge 
and  floating  in  it  are  stringy  masses  of  fibrin,  some  of  which  are  very 
short  and  others  two  or  more  centimetres  in  length.  Visceral  peri- 
toneum is  smooth  and  glistening.  Appendix  is  12  cm.  long  and  has  a 
mesentery  which  reaches  to  the  tip.  It  is  curled  about  the  caecum  so 
that  the  tip  lies  to  the  inside  and  in  front  of  the  caecal  wall.  The  mesen- 
tery contains  an  enormous  amount  of  fat.  The  lymph  nodes  are  not 
enlarged.  Diaphragm,  left  sixth  rib,  right  fifth  rib. 

Pleura!  cavities.  On  the  left  side  the  pleura  is  smooth  glistening 
and  deep  red  in  color.  On  the  right  the  pleura  is  very  adherent  by  old, 
dense  adhesions. 

Pericardia!  cavity.  It  is  rather  large  and  contains  a  slightly  larger 
amount  of  fluid  than  usual.  The  smaller  vessels  stand  out  very  clearly 
on  the  parietal  layer.  There  are  several  white  thickened  areas  on  the 
visceral  layer. 

Heart.  Weight  410  grams.  The  coronary  arteries  are  conspicuous. 
On  section  their  walls  are  thick  and  very  stiff.  The  intima  is  yellow 
and  in  some  areas  quite  hard.  The  heart  muscle  is  deep  red  in  color  and 
firm  to  the  touch.  Valves  are  slightly  and  uniformly  thickened  and 
yellow  in  color.  The  aortic  ring  has  bulging  from  its  margin  into  the 
lumen  several  large  projections  which  are  hard  and  wart-like.  They  are 
gritty  and  sound  like  bone  when  tapped  with  the  scalpel  handle. 

Lungs.  Left:  has  a  very  deep  red  color.  Crepitation  in  somewhat 
decreased.  On  section  it  contains  a  great  deal  of  dark  red  fluid  which 
can  be  expressed  as  red  foam.  The  bronchi  and  bronchial  glands  are 
negative. 

Right:  external  surface  presents  a  very  shaggy  appearance.  On 
section  it  is  similar  to  the  left  save  that  there  seems  to  be  a  little  less  fluid 
and  the  lung  has  a  very  distinct  brown-red  color. 

Spleen.  Weight  310  grams,  of  firm  consistency  and  white  color. 
Organ  is  gray  in  color.  On  section  the  capsule  and  trabeculae  are 
thickened.  The  follicles  are  not  visible.  Capsule  is  grayish  brown  in 
color. 


388  PATHOLOGY 

Gastrointestinal  tract.  The  colon  is  dilated  and  contains  a  gray-green 
fluid.  The  walls  are  very  dark  red.  There  is  no  ulceration. 

Pancreas.  It  is  rather  large  and  is  yellow  from  the  great  amount  of 
fat  in  which  it  is  embedded. 

Liver  weighs  1900  grams.  It  is  extremely  firm,  preserves  its  shape 
when  laid  on  the  table,  shows  somewhat  rounded  edges  and  a  moderately 
thickened,  opaque  capsule.  The  surface  shows  projecting  yellowish- 
brown,  relatively  soft  nodules,  averaging  from  3  to  5  mm.  in  diam- 
eter and  separated  by  firm  gray  depressed  bands  of  connective  tissue. 
The  organ  cuts  with  leathery  resistance  and  shows  a  generally  re- 
tracted cut  surface,  in  which  lobular  markings  are  not  preserved, 
but  showing  a  slightly  projecting  yellowish-brown  parenchyma  and  a 
retracted  network  of  gray  scar  tissue.  Gall  bladder  and  ducts  are 
normal. 

Kidneys.  Weight  400  grams.  Several  small  cysts  can  be  seen  on 
the  surface  and  one  or  two  depressions  are  seen  near  the  poles.  The 
capsules  strip  with  difficulty  leaving  the  surface  slightly  granular.  The 
stellate  veins  are  prominent.  The  cortex  measures  from  6  to  8  mm. 
and  in  places  is  distinctly  yellow.  The  glomeruli  can  be  seen  as  glisten- 
ing dots.  The  pyramids  are  closely  outlined. 

Adrenals  negative. 

Bladder  negative. 

Genital  organs  negative. 

Aorta.  The  arch  is  stiffened  by  a  deposit  of  yellowish,  gritty  material 
and  in  one  area,  i  cm.  in  diameter,  there  is  a  shallow  excavation  which  has 
a  jagged  border  of  very  hard  material.  The  floor  of  this  patch  is  rough- 
ened and  yellow  green  in  color.  The  descending  portion  of  the  thoracic 
aorta  is  thickened  and  there  are  long,  raised,  yellow  patches  beneath  the 
intima.  The  abdominal  aorta  has  a  greater  number  of  patches  than  the 
thoracic  and  the  rings  about  the  intercostal  branches  contain  calcareous 
material. 

REMARKS.  The  liver  is  larger  than  is  usual  in  this  type  of  cirrh- 
osis, but  the  size  may  vary  greatly.  The  enormous  ascites  is  due 
to  the  long  standing  obstruction  to  the  portal  circulation.  The 
enlarged  and  fibrous  spleen  is  characteristic.  The  heart  hyper- 
trophy is  due  both  to  the  chronic  diffuse  nephropathy  and  to  the 
calcification  of  the  aortic  valves  which  slightly  obstructed  the  out- 
let. Such  valvular  changes,  as  here  described,  are  due  to  the  exten- 
sion to  the  valves  of  the  sclerosis  of  the  aorta  and  not  to  a  preceding 
acute  endocarditis. 


THE  PATHOLOGY  OF  THE  LIVER  389 

EXPERIMENTS.  Experimental  focal  necrosis  of  the  liver  has  been 
studied  in  connection  with  the  experiments  on  blood  destruction  (see 
p.  69)  and  those  on  necrosis  (see  p.  43).  A  similar  condition  can  be 
produced  by  injecting  0.5  c.c.  ether  into  the  posterior  auricular  vein 
of  a  rabbit  or  2.0  c.c.  ether  into  the  jugular  vein  of  a  cat.  Histologic 
sections  are  to  be  made  24  hours  later.  Of  interest  is  the  jaundice 
produced  by  the  ligature  of  the  common  bile  duct  of  the  dog, 
studying  the  general  jaundice,  pallid  stools  and  the  pigmentation 
of  the  urine.  Experimental  cirrhosis  is  best  produced  by  ligating 
the  common  duct  of  a  rabbit  and  performing  the  autopsy  at  the 
end  of  4  weeks.  Striking  gross  and  histological  pictures  are 
obtained. 


389  a 


389b 


389c 


389d 


THE  PATHOLOGY  OF  THE  LUNGS 

Infection  plays  the  dominant  role  in  the  production  of  lesions 
in  the  lungs.  Certain  of  the  infections  and  other  lesions  have 
already  been  considered  (see  particularly  Lobar  Pneumonia,  page 
225).  While  many  of  the  lung  infections  are  primary,  yet  when  the 
infections  are  considered  as  a  whole,  probably  the  most  are  second- 
ary to  infection  elsewhere,  which  may  supply  the  infectious  agents, 
produce  conditions  which  facilitate  their  entry  into  the  tissue,  or 
lower  the  general  resistance.  In  most  of  the  secondary  infections, 
the  three  conditions  act  together. 

BRONCHO-PNEUMONIA.  The  most  important  of  the  secondary 
infections  is  broncho-pneumonia  (catarrhal  pneumonia,  lobular 
pneumonia).  The  disease  is  much  more  common  hi  children  than 
in  adults,  so  common  that  it  is  found  in  more  than  half  of  all  autop- 
sies of  children  under  two  years  of  age.  The  lesions  consist  in  the 
presence  of  foci  of  inflammation  in  the  lung,  in  relation  to  the 
bronchi,  representing  the  results  of  the  action  of  injurious  substances 
which  enter  the  lung  by  means  of  the  bronchi.  The  foci  may  be  few 
in  number,  or  they  may  be  very  numerous  and  evenly  distributed 
through  the  tissue.  The  lower  lobes  and  the  posterior  portions 
of  the  lungs  are  more  frequently  affected  than  are  the  upper  lobes 
and  the  anterior  portions.  The  exudate  fills  the  alveoli  in  the 
affected  areas;  these  may  be  felt  as  hard  shot-like  areas  and  appear 
on  section  as  slightly  projecting  areas  which  usually  are  somewhat 
paler  than  the  general  parenchyma.  The  character  of  the  exuda- 
tion varies,  to  some  extent,  with  the  character  of  the  injurious  agent, 
and  may  be  serous,  purulent,  haemorrhagic  or  fibrinous,  the  last 
being  as  definite  as  in  lobar  pneumonia.  With  the  exudation  there 
often  are  found  in  the  alveoli  numbers  of  the  large  cells  of  endothe- 
lial  character,  the  presence  of  which  has  given  rise  to  the  synonym 
catarrhal  pneumonia,  a  term  happily  falling  into  obsolescence. 
Large  areas  of  solidification,  two  or  more  centimeters  in  diameter, 
may  be  produced  by  confluence  of  small  foci,  or  without  confluence 
these  may  be  so  closely  set  as  to  give  the  impression  of  extensive 
solidification;  portions  cut  from  such  areas,  however,  do  not  sink 

39° 


THE  PATHOLOGY  OF  THE  LUNGS         391 

in  water.  Entire  lobules  of  the  lung  may  be  affected,  this  giving 
rise  to  the  synonym  "lobular  pneumonia."  By  "lobule"  in  this 
connection  is  understood  not  the  histological  lobule  into  which  the 
terminal  bronchus  enters,  but  the  anatomical  lobule  which  contains 
in  the  neighborhood  of  one  hundred  such  terminal  units  and  is 
indicated  on  the  pleural  surface  by  the  field  separated  by  the  lines 
of  the  pleural  lymphatics.  The  histogenesis  of  the  process  can  be 
studied  best  in  areas  from  an  affected  part,  which  present  no  lesions 
to  the  naked  eye.  In  such  tissues  foci  may  be  seen  hi  which  the 
exudation  is  confined  to  the  atrium  and  from  this  primary  point 
of  infection  the  process  extends.  Extension  to  neighboring  lobules 
through  the  alveolar  walls  does  not  take  place  to  any  considerable 
degree,  the  extension  being  rather  by  the  continuous  involvement 
of  other  terminal  bronchi  and  of  their  related  alveoli.  The  pleura 
may  be  affected,  but  not  so  frequently,  nor  to  the  same  degree,  as 
in  lobar  pneumonia. 

There  is  no  single  setiological  agent.  The  streptococci,  the  pneu- 
mococci,  the  staphylococci  are  found  in  almost  equal  frequency, 
and  the  same  organism  may,  hi  different  cases,  produce  all  the  varied 
forms  of  exudation. 

ASPIRATION  PNEUMONIA.  Another  form  of  pneumonia  is  that 
which  is  known  as  aspiration  pneumonia  or  foreign  body  pneumonia. 
It  is  produced  by  substances,  such  as  food  or  foreign  bodies  of  any 
sort,  which  are  aspirated  into  the  bronchi  and  alveoli,  or  both,  and 
which  produce  foci  of  inflammation  about  them.  The  foci  are 
most  frequent  in  the  lower  lobes  and  there  is  usually  an  acute 
inflammation  of  the  afferent  bronchus.  The  exudate  is  usually 
purulent  and  there  is  a  marked  tendency  to  abscess  formation  and 
gangrene. 

HYPOSTATIC  PNEUMONIA  appears  most  commonly  in  the  pos- 
terior portion  of  the  lower  lobes  of  the  lung,  an  infection  being 
added  to  passive  hyperaemia.  The  condition  appears  by  preference 
in  the  course  of  severe  and  long  continued  infections,  such  as  typhoid 
fever.  The  exudate  is  not  abundant  and  contains  few  cells,  other 
than  red  blood  corpuscles,  and  usually  little  or  no  fibrin. 

In  acute  interstitial  pneumonia  the  interlobular  septa  of  the 
lung  are  enlarged  and  pale  and  the  consistency  of  the  lung  increased. 
It  is  due  to  infection  of  the  lung  by  way  of  the  interlobular  lympha- 
tics. In  the  interlobular  tissue  there  is  a  purulent  or  fibrino-puru- 


392  PATHOLOGY 

lent  exudate  which  extends  into  the  adjoining  alveoli.  The 
interlobular  tissue  may  be  involved  in  the  course  of  both  lobular  and 
lobar  pneumonia.  When  it  arises,  as  an  independent  affection,  it 
usually  extends  into  the  lung  from  the  pleura  and  is  most  marked  on 
the  pleural  surface.  It  is  an  uncommon  condition  and  usually  is 
due  to  infection  with  pyogenic  cocci.  In  the  chronic  form  of  inter- 
stitial pneumonia  the  exudate  may  be  replaced  by  fibrous  cica- 
tricial  tissue. 

ATELECTASIS  OF  THE  LUNG.  In  atelectasis  of  the  lung  there  is 
collapse  of  the  air  spaces,  due  to  diminution  or  disappearance  of  the 
air  content.  The  collapsed  portions  of  the  lung  are  depressed  below 
the  surface  and  deeply  cyanotic.  Two  forms  of  this  are  recognized: 
(a)  foetal  atelectases  in  which  the  post-partum  distension  of  the  lung 
does  not  take  place;  and  (6)  acquired  atelectases  of  which  there  are 
two  forms,  one,  compression  atelectasis,  arising  from  compression 
of  the  lung  from  without,  due  to  the  collection  of  fluid  or  air  or  the 
presence  of  tumors  in  the  pleura]  cavity,  and  the  other,  occlusion 
atelectasis,  due  to  the  occlusion  of  bronchi  by  secretion,  exudation, 
foreign  bodies,  etc.  The  air,  which  is  retained  in  the  lung  supplied 
by  the  closed  bronchi,  becomes  absorbed  and  the  alveoli  collapse. 

EMPHYSEMA.  An  increase  in  the  air  content  of  the  lung  is  desig- 
nated as  emphysema  and  of  this  two  forms,  vesicular  and  inter- 
stitial emphysema,  can  be  distinguished,  depending  upon  whether 
the  air  is  contained  in  the  dilated  alveoli,  or  in  the  interstitial  tissue 
of  the  lung.  Interstitial  emphysema  is  due  to  rupture  of  the  lung 
with  the  escape  of  the  air  into  the  interstitial  tissue.  The  condition 
makes  itself  manifest  on  the  pleural  surface  in  the  form  of  small 
bubbles  of  air  in  the  interlobular  septa;  on  pressure  the  tissue 
crackles  beneath  the  fingers  and  the  bubbles  can  be  moved  along. 
In  marked  conditions  of  interstitial  emphysema  the  air  passes  from 
the  hylum  of  the  lung  into  the  mediastinum  and  from  this  by  way 
of  the  cervical  fascia  into  the  subcutaneous  tissue.  It  may  also 
pass  more  directly  when  there  are  pleuritic  adhesions  (see  page  264). 

EXPERIMENTS.  The  study  of  experimental  conditions  of  the 
lungs  and  thorax  include  certain  experiments  in  inflammation 
already  taken  up,  the  various  forms  of  pleurisy.  The  production  of 
pneumothorax  by  the  injection  of  500  c.c.  air  into  the  thorax  of 
an  anaesthetized  dog  can  be  studied  by  observing  the  effect  on 
respiration  and  blood  pressure  as  indicated  by  the  kymograph. 


THE  PATHOLOGY  OF  THE  LUNGS         393 

The  trachea  should  be  clamped  before  opening  the  thorax  at 
autopsy  so  as  to  show  the  atelectasis  of  the  lungs.  The  experi- 
ment can  be  repeated,  using  salt  solution  or  olive  oil  instead  of  air, 
with  the  production  of  hydrothorax.  Asthma  is  studied  in  the 
clinical  manifestations  of  immediate  anaphylaxis  in  the  guinea  pig 
and  later  studying  the  underlying  acute  emphysema.  (Edema  of 
the  lungs  (usually  associated  with  haemorrhage)  can  be  produced 
by  the  injection  into  the  posterior  auricular  vein  of  a  rabbit  of 
0.7  c.c.  i :  1000  adrenalin  solution.  Acute  bronchitis  can  be  pro- 
duced in  the  cat  by  the  inhalation  through  a  tracheal  cannula  of 
the  fumes  of  strong  ammonia.  The  physical  signs  are  studied, 
especially  with  the  multiple  stethoscope  (rales)  and  the  autopsy 
performed  to  show  the  acute  inflammatory  process. 


393 


393  b 


393 


393d 


393  e 


STUDENTS'  INDEX 


STUDENTS'  INDEX 


STUDENTS'  INDEX 


STUDENTS'  INDEX 


STUDENTS'  INDEX 


STUDENTS'  INDEX 


INDEX 


A. 

Abortion,  220. 
Abscess,  50. 

amoebic,  313. 

cavity,  211. 

formation,  203,  211. 

healing,  212. 

membrane  pyogenic,  211. 

metastatic,  213. 

multiple,  213. 

subcutaneous,  105,  213. 
Actinomycosis  bovis,  280. 
Adaptation,  60,  194. 
Addison's  disease,  37. 
Adenoma,  162. 

adenocarcinoma,  166. 

adenocystoma,  163. 

adenofibroma,  151. 

papilliferous,  163. 
Adrenal  gland,  accessory,  172. 

carcinoma  metastatic,  179. 

lymphoma  metastatic,  184. 
Albuminuria,  160,  349. 
Alexine,  199. 
Algor  mortis,  41. 
Alimentary  canal,  365. 

experiments,  371. 

snake  venom,  370. 
Amboceptor,  199. 
Amyloid,  31. 

degeneration,  267. 

local  formation,  33. 
Anaemia,  60,  305,  358. 

pernicious,  61. 

secondary,  61,  179. 
Anasarca,  93,  95,  97,  100,  362. 
Aneurysm,  80. 

aorta,  118,  120,  121. 

cirsoid,  80. 

dissecting,  81. 

diffuse,  80. 


Aneurysm,  continued. 
miliary,  8l,  275. 
rupture,  1 1 8. 
saccular,  80. 
spindle  form,  80. 
tuberculous,  248. 
Anhydraemia,  62. 
Ankylostoma  duodenale,  333. 
Anthrax,  285. 

carbuncle,  285,  286. 
Antigen,  2OO. 
Antitoxin,  200. 

Appendix,  appendectomy,  310. 
appendicitis,  120,  366. 
cystic  dilatation,  121. 
tuberculous,  262. 

Arteriosclerosis,  81,  97,  108,  113,  115, 
118,    121,    172,    177,   227,   232, 
267,  275,  362. 
atheromatous  ulcer,  78. 
calcification,  78. 
Artery,  76. 

coronary,  sclerosis,  113,    367. 
coronary,  thrombosis,  115. 
Ascites,  93,  95,  100,  115,  362,  387. 
Atrium  of  infection,  204. 
Atrophy,  26. 

from  malnutrition,  26. 
from  pressure,  27. 
from  disuse,  27. 
neuropathic,  27. 
senile,  27. 
Autolysis,  53. 

Autopsies,  95,  97,  100,  105,  108,  lit, 
113,  115,  118,  120,  121,  172,  175, 
177, 184,  187,  192,  213,  218, 220, 
227,  229,  232,  237,  239,  262, 263, 
266,  267,  275,  280,  282,  286,  292, 
299.  3<>3.  305,  3io,  314,  319,  322, 
326,  329.  358,  367,  374.  382, 
386. 


395 


396 


INDEX 


B. 

Bacilli,  195. 
Bacillus,  anthracis,  285. 

anthracis  septicaemia,  286. 

coli  communis,  276,  310. 

diphtheria,  290. 

dysenterse,  315. 

mallei,  282. 

tuberculosis,  243. 
Bacteria,  195. 
Bacteriolysis,  199. 
Bile  ducts,  260. 

cholangitis,  310,  374. 
Bilharzia  Haematobium,  142. 
Bilirubin,  38. 
Biliverdin,  38. 

Bladder,  urinary,  cystitis,  275. 
Blood,  60. 

coagulation,  62. 

changes  in  malaria,  318.  ' 

experiments  on,  69. 

formation  of,  24. 

platelets,  63. 

tumors,  159. 

vessels,  new  formation,  53. 
Body,  general  structure,  19. 
Bone,  regeneration,  130. 

tuberculosis,  260. 
Bone  marrow,  179. 

hyperplasia,  179,  358. 

lymphoma  metastatic,  184. 
Brain,  91. 

abscess,  221. 

carcinoma  metastatic,  175. 

congestion,  232. 

cyst,  97. 

haemorrhage,  97. 

oedema,  362. 

passive  congestion,  91. 
Breast,  carcinoma,  175. 
Bronchi,  bronchitis,  121,  172,  322,  326. 

bronchitis,  tuberculous,  251. 
Bronchioliths,  37. 
Bronchopneumonia,     226,     276,     292, 

326,  390. 


C. 


Cachexia,  139. 
Calcification,  35. 
Calculi,  36. 
biliary,  36. 


Calculi,  continued. 

pancreatic,  36. 

salivary,  36. 

urinary,  36. 

Capsule  formation,  195. 
Carbuncle,  212. 
Carcinoma,  163. 

adenocarcinoma,  166. 

anaemia  from,  179. 

baso-cellulare,  165. 

breast,  175. 

colloid,  1 66. 

cylindrical  cell,  166. 

en  cuirass,  175. 

epidermoid,  164,  165. 
keratin  formation,  165. 
pearls,  165. 
rodent  ulcer,  166. 

epithelial  fibrils,  165. 

glandular,  166. 

medullary,  164. 

pleura,  175. 

scirrhous,  164. 

stomach,  177. 

ulceration,  175,  176. 
"Carriers,"  206. 
Cases,  171,  175,  182,  183,  234. 
Cell,  endothelial,  56. 

plasma,  56. 

structure,  17. 
Cestodes,  331. 
Chemotaxis,  52. 
Chemotropism,  52. 
Chloroma,  160. 
Cholera,  309. 
Cholesteatoma,  169. 
Cholesterin,  31. 
Chondroma,  152. 

chondrosarcoma,  153. 
Chorio-epithelioma,  166. 
Choroid  plexus,  cyst,  232,  374. 
Circulation,  82. 

experiments  on,  82. 

pathological  physiology  of,  84. 
Cloudy  swelling,  29. 
Coagulation  necrosis,  43. 
Coliquation  necrosis,  43. 
Colloid  degeneration,  34. 
Colon,  amoebic,  dysentery,  314. 
acute  epidemic  dysentery,  306. 

necrosis,  305. 


INDEX 


397 


Colon,  continued. 

perforation,  314. 

ptosis,  172. 

typhoid  ulcer,  303. 

ulceration,  305. 
Complement,  199. 
Concretion,  36. 

intestinal,  37. 

preputial,  37. 
Condyloma,  broad,  272. 
Congestion,  passive,  89,  95,  97,   108, 

US- 

Conjunctiva,  acute  conjunctivitis,  303. 
Corpora  amylacea,  35. 
Crisis,  205. 
Cyanosis,  88. 

Cyclasterion  scarlatinalis,  326. 
Cysts,  147. 

congenital,  147. 

dermoid,  147,  169. 

epidermoid,  169. 

extravasation,  147. 

exudation,  147. 

kidney,  147. 

retention,  147. 

softening,  147. 
Cytoryctes  variolae,  321. 
Cysticercus  cellulosa,  332. 

D. 

Defervescence,  205. 
Degeneration,  29. 

cloudy  swelling,  29. 

experimental,  44. 

hyalin,  33. 

hydropic,  33. 

parenchymatous,  286,  292,  299. 

vacuolar,  33. 

Zenker's,  34. 
Diabetes,  267. 

bronze,  373. 
Diapedesis,  47. 
Dibothriocephalus  latus,  331. 
Diphtheria,  290. 

bronchopneumonia,  291. 

lesions,  290. 

membrane,  290,  292. 

mixed  infection,  291. 
Diplococcus      intracellularis      menin- 

gitidis,  235. 
Diplococcus  lanceolatus,  224. 


Diplococcus  pneumonia,  224. 

Disease,  17. 

Distomata,  334. 

Dropsy,  93. 

Duct  of  Wirsung,  concretion  in,  374. 

Dysentery,  305. 

amoebic,  314. 

diphtheritic,  305. 

epidemic,  305. 

E. 
Ear,  otitis  media,  105,  220,  227,  229, 

232,  326. 

Ecchymoses,  92,  184. 
Eclampsia,  44. 
Embolism,  66,  108,  310. 

air,  68. 

fat,  68. 

paradoxical,  66. 

parenchymatous,  68. 
Embryoma,  171. 
Emigration,  47. 
Emphysema,  186. 
Empyema,  218. 
Endocardium,  74. 

endocarditis,  chronic,  213. 

endocarditis,  74,  95,  97,   100,   105, 
172,  239. 

thrombosis,  115. 
Endometritis,  218. 
Endothelioma,  154. 
Endotoxins,  196. 
Entamceba  histolytica,  313. 
Ependymitis,  granular,  267. 
Epicardium,  71. 

ecchymoses,  97. 

lymphoma  metastatic,  184. 
Epididymis,  tuberculous,  255,  267. 
Erysipelas,  200. 

F. 
Fallopian  tubes,  gonorrheal,  238. 

tuberculosis,  255. 
Fat  necrosis,  43,  374. 
Fatty  degeneration,  29. 
Fastigium,  205. 
Fibroblasts,  57. 
Fibro-lipoma,  151. 
Fibroma  durum,  149. 

fibrochondroma,  153. 

fibroepithelium,  150. 

intracanalicular,  151. 


INDEX 


Fibroma  durum,  continued. 
keloid,  149. 
i  nolle,  149. 

neuro,  149. 
Fibrosarcoma,  150. 
Flukeworms,  334. 
Furuncle.  212. 

G. 
Gall  bladder,  cholecystitis,  310,  374. 

cholecystotomy,  374. 
Gall  atones,  36. 
Gangrene,  44,  108. 
Genitalia,  tuberculosis,  254. 
Genito-urinary    system,    tuberculosis, 

266. 
Glanders,  282. 

abscess  formation,  282. 

pustules,  282. 
Glioma,  157. 
Gliosis,  263. 
Gluge's  corpuscles,  31. 
Glycogen,  31. 

glycogenic  degeneration,  267. 
Glycosuria,    experimental    production, 

377- 

Gonococcus,  238. 
Gonorrhea,  238. 
Gout,  40. 

Granulation  tissue,  53. 
Growth,  124. 

H. 

Haemangioma,  154. 
Haematin,  38. 
Haematoidin,  38. 
Hsematoma,  92. 
Haemochromatosis,  38. 
Haemoglobin,  37. 
Haemoglobinaemia,  38,  62. 
Haemoglobinuria,  62. 
Haemolysis,  62. 
Haemolysin,  196. 
Haemorrhage,  374. 
Haemosiderin,  38. 
Heart,  71. 

aneurysm,  108. 

dyspnoea,  88. 

fatty  degeneration,  181,  326. 

hypertrophy,   74,   86,   97,   IOO,   108, 
"5.  275,  385,  386. 


Heart,  continued. 

infarction,  87,  115. 

insufficiency,  88. 

perforation,  239. 

rhabdomyoma,  142,  158. 

thrombi,  115,  108,  326,  75. 

valves,  insufficiency,  85. 

stenosis,  85. 
Heredity,  206. 
Hernia,  112. 
Hormones,  125. 
Hydraemia,  62. 
Hydropericardium,   93,   95,    100,    115, 

232. 
Hydrothorax,   93,   95,    100,    115,    121, 

362. 

Hyperplasia,  124. 
Hypertrophy,  124. 
Hypoleukocytosis,  52,  125. 
Hypoplasia,  26. 

I. 

Ileum,  dysenteric  lesions,  306. 
haemorrhage,  189. 
perforation,  108,    303. 
tuberculous  ulcer,  254. 
typhoid  ulcer,  299. 
Immunity,  201. 
Incrustation,  36. 
Incubation,  205. 
Infarction,  67. 
red,  67. 
uric  acid,  347. 
white,  67. 
Infection,  194,  196. 
atrium  of,  204. 
chronic,  204. 
from  conjunctiva,  197. 

intestinal  canal,  198. 
lungs,  197. 
middle  ear,  197. 
mouth,  197. 
nasal  passages,  197. 
oesophagus,  198. 
skin,  197. 
stomach,  198. 
tonsil,  197. 
wounds,  198. 
intra-uterine,  207. 
multiple,  275. 
post  partum,  218. 


INDEX 


399 


Infection,  coniimied 

secondary,  207. 

terminal,  207. 

variation  in,  208. 
Infectious  diseases,  194. 

experiments,  334. 
Infestation,  194. 
Inflammation,  46. 

catarrhal,  50. 

experiments,  58. 

exudation,  48. 
diphtheritic,  50. 
fibrinous,  49. 
haemorrhagic,  50. 
purulent,  50. 
serous,  49. 

heat,  47. 

pain,  50. 

purulent  infiltration,  187. 

redness,  47. 

swelling,  48. 
Intestine,  carcinoma  metastatic,  179. 

dysentery,  305,  314. 

lymphoma  metastatic,  184. 

passive  congestion,  91. 

pathology  of,  365  -  371. 

perforation,  108,  303,  314. 

tuberculosis,  256,  263. 

typhoid  lesions,  299. 
Invasion,  205. 
Involucrum,  212. 

J. 
Jaundice,  39,  310,  374,  382,  286. 

K. 

Karyolysis,  43. 
Karyorhexis,  43. 
Keloid,  149. 
Keratitis,  203. 
Kidney,  337. 

albuminuria,  349. 

arteriosclerosis,  344,  j5/. 

atrophy,  356. 

blood  vessels,  337. 

cantharadin,  effects  on,  364. 

congestion,  386. 
passive,  90. 

cysts,  172. 

decapsulation,  358. 

double  pelvis,  172,  369. 


Kidney,  continued. 
embryoma,  171. 
experiments,  364. 
gout,  355. 

granular  contracted,  355. 
haemorrhage,  344. 
hydronephrosis,  172,  344. 
hyper  asm  ia,  acute,  343. 

passive,  343. 
infarction,  97,  115,  344. 

bilirubin,  348. 

uric  acid,  347. 
lymphoma  metastasis,  184. 
malformations,  340. 
mercuric  iodide,  effects  on,  364 
mixed  tumor  of,  171. 
nephropathy,  108,  115,  172,  343 

acute  capsular,  353. 

acute  diffuse,  350. 

acute  interstitial,  291,  326,  350. 

acute  intracapillary,  352. 

chronic,  353,  358, 

chronic  diffuse,  355. 

chronic  interstitial,  355. 

degenerative,  345. 

desquamative,  348. 

diffuse,  386. 

infectious,  345. 

obstructive,  344. 

glomerular,  100,  352. 
acute,  220,  218. 
intracapillary,  362. 

parenchymatous,  352. 

subacute,  353. 

vascular,  343. 
nephrolithiasis,  345. 
nephrophthisis,  256. 
pathology  of  337  -  364., 
potassium     chromate     effects,    on, 

363. 
pyelonephritis,  345,  310. 

tuberculous,  256,  276. 
tuberculosis,  256. 
uranium  nitrate,  364. 

L. 
Larynx,  cedema,  97. 

laryngitis,  322. 
Lead  poisoning,  40. 
Leiomyoma,  153. 
Leprosy,  270. 


400 


INDEX 


Leukaemia,  160. 

lymphatic,  160. 

myelogenous,  161,  187. 
Lip,  epidermoid  carcinoma.'ljl. 
Lipochrome,  37. 
Lipoma,  151. 
Liver,  abscess,  310. 

amoebic,  314. 

acute  yellow  atrophy,  378,  382. 

carcinoma  metastatic,  179. 

cirrhosis,  90,  100,  380,  386. 
atrophic,  380. 
cardiac,  90,  380. 
hypertrophic,  381. 
monolobular,  380. 
multilobular,  380. 

congestion,  172. 
passive,  90. 

experiments,  390. 

lymphoma  metastatic,  184. 

leukaemia,  187. 

necrosis,  43,  95,  305. 
chloroform,  129. 
focal,  220,  326. 

nutmeg,  90. 

pathology  of,  378. 

perihepatitis,  97,  100,  172. 

regeneration,  128. 

tuberculosis,  260,  262. 
Livor  mortis,  41. 
Liquefaction  necrosis,  43. 
Lung,  abscess,  106,  187,  213,  218. 

anthracosis,  314. 

atelectasis,  121,  392,  393. 

bronchopneumonia,  121. 

bronchitis,  121. 

carnification,  226. 

coal  miner's,  39. 

congestion,  172,  213. 

embolus,  112. 

emphysema,  100,  184,  314,  392. 

engorgement,  225. 

experiments,  392. 

hepatization,  225. 

infarction  of,  95,  97,  105,  108,  115, 
213. 

lymphoma  metastatic,  184. 

oedema,  176,  299,305,  322,  362,  367, 
386. 

pathology  of,  390. 

pneumonia,  (see  pneumonia). 


Lung,  tuberculosis,  172,  176,  249,  262. 

Lupus,  261. 

Lymph  nodes,  haemorrhage,  103. 

lymphnoditis  acute,  286. 

metastatic  carcinoma,  179. 

syphilis  of,  272. 

tuberculosis,  173,  257,  263. 

typhoid,  300. 
Lymphangioma,  154. 
Lymphatics,  160. 
Lymphoma,  159,  184. 

metastasis,  184. 
Lysis,  205. 

M. 

Macrocheilia,  154. 
Macrogamete,  318. 
Macroglossia,  154. 
Macrophage,  55. 
Malaria,  317. 

chronic,  305,  306. 

pernicious,  319. 

pigment  formation,  318. 
Mastoid,  mastoiditis,  105,  220,  276. 
Measles,  325: 

skin  eruption,  325. 
Mediastinum,  emphysema,  264. 

mediastinitis,  322. 
Membrana  propria,  162. 
Meninges,  meningitis,  220,  229. 

haemorrhagic,  286. 

epidemic  cerebro-spinal,  235,  237. 

tuberculous,  259,  262. 
Merozoites,  318. 
Metaplasia,  130. 
Metastases,  164. 
Methsemoglobin,  38. 
Metritis,  218. 
Microgamete,  318. 
Microphage,  55. 
Milzbrand,  285. 
Mitosis,  124. 
Mole  hydatidiform,  167. 
Moulds,  195. 
Mucoid  degeneration,  32. 
Muscle,  regeneration,  129. 
Myocardium,  73. 

abscess,  73. 

aneurysm,  74. 

fatty  degeneration,  73. 

hyalin  degeneration,  73. 


INDEX 


401 


Myocardium,  continued. 

myocarditis,  108,  no,  113,  239,  367. 
fibrous,  73. 

necrosis,  73. 

tubercle,  73. 
Myoma,  uterus,  176. 
Myxoma,  151. 

myxochondroma,  152. 
Myeloma,  160. 

N 

Naevus,  154. 
Necrosis,  41. 

fat,  43. 

liver,  43. 
Nematodes,  332. 
Nerves,  neuroma,  149. 

regeneration,  128. 
Neuro-epithelioma,  157. 
Neurofibroma,  149. 
Neuroglia,  cell  proliferation,  235. 
Neuroma,  157.  • 

multiple,  149. 

plexiform,  150. 
Nipple,  retraction,  175. 

O. 

Ochronosis,  37. 
(Edema,  93,  115,  386. 

cardiac,  94. 

larynx,  97. 

renal,  95. 

subpial,  374. 

tissue  changes,  94. 
(Esophagus,  carcinoma,  172. 

penetration  by  tumor,  172. 

smallpox,  322. 

stricture,  172. 

ulceration,  173. 
Oligaemia,  60. 
Oligocythsemia,  60. 
Omentum,  metastatic  carci.ioma,  179. 
Onchosphere,  331. 
Ookinet,  318. 
Opsonins,  199. 
Osteoclasts,  130. 
Osteochondritis  syphilitica,  274. 
Osteoma,  153. 
eburneum,  153. 
spongiosum,  153. 
Osteomyelitis,  212. 


Otitis  media,  220,  227,  229,  232,  326. 
Ovary,  metastatic  carcinoma,  179. 

P. 

Pancreas,  372. 

abscess,  372. 

atrophy,  373. 

calculi,  374. 

carcinoma  metastatic,  179 

degeneration,  373. 

diabetes,  373. 
bronze,  373. 

experiments,  377. 

necrosis,  373. 

pancreatitis,  chronic,  100,  172. 
acute  haemorrhage,  374. 
gangrenous,  374. 
purulent,  374. 

secretion,  373. 

structure,  372. 

syphilis,  372. 

tuberculosis,  372. 
Papilloma,  150. 
Parametrium,  219. 
Parasite,  194. 
Pediculi,  194. 
Penis,  sarcoma,  183. 
Pericardium,  haemorrhage,  239. 

pericarditis,  72,  239,  329. 
Perihepatitis,  172. 
Perithelioma,  156. 

Peritoneum,     carcinoma     metastatic, 
179. 

peritonitis,    acute,    108,    303,    314, 

367,  374- 
amrebic,  314. 

chronic,  113,  232,  275,  386. 
Petechiae,  92,  184. 
Peyer's  patch,  typhoid,  301. 
Phagocytosis,  53,  54,  199. 
Pharynx,  97. 

smallpox,  322. 

ulceration  in  typhoid,  301. 
Phlebitis,  76,  101. 
Phleboliths,  37. 
Phthisis,  252,  262. 

fibroid,  253. 

tuberculous,  267. 
Pia  mater,  oKlema,  97. 
Pigmentation,  37. 

autochthonous,  37. 


402 


INDEX 


Pigmentation,  continued. 

extraneous,  39. 

haematogenous,  38. 

malarial,  37. 
Placenta,  syphilis,  274. 
Plasmodium  malaria?,  317. 

precox,  317. 

vivax,  317. 
Plethora,  62. 
Pleura,  carcinoma,  175. 

pleuritis  chronic,  97,  121,  175,  179, 
213,  266,  267,  276,  367, 
386. 

pleuritis  acute,  227,  229,  232, 
282. 

tuberculosis,  262,  266. 
Pneumococcus,  224,  326. 
Pneumonia,  aspiration,  391. 

caseous,  251. 

catarrhal,  390. 

croupous,  232. 
acute,  225,  227. 

hypostatic,  391. 

interlobular,  391. 

interstitial,  acute,  391. 

in  cerebro-spinal  meningitis,  236. 

leucocytosis,  227. 

lobar,  acute,  225. 

lobular,  390. 

organizing,  226,  229,  232. 

resolution,  226. 

syphilitic,  274. 

tuberculous,  267,  251. 

unresolved,  229. 
Pneumothorax,  263,  392. 
Poliomyelitis,  acute  anterior,  329. 

lesions,  329. 

virus  of,  329. 
Polypi,  150. 
Post  mortem,  42. 

blood  coagulation,  42. 

cell  changes,  42. 

decomposition,  42. 

putrefaction,  42. 
Pott's  disease,  261. 
Prostate,  prostatitis  acute,  239,  275. 
Protozoa,  195. 
Pus,  211. 

Pylephlebitis,  310. 
Pyknosis,  43. 
Pylorus,  occlusion,  179. 


R. 

Recovery,  206. 
Regeneration,  124. 
Repair,  52,  55. 
Resolution,  226. 
Rhabdomyoma,  158. 
Ribs,  metastatic  carcinoma,  17.;. 
Rigor  mortis,  41. 

S. 
Salpingitis,  acute,  234. 

gonorrhceal,  238. 
Saprophyte,  206. 
Sarcoma,  155. 

giant  cell,  156. 

melanotic,  182,  157. 

mixed  cell,  156. 

osteo,  156. 

osteoid,  156. 

penis,  183. 

round  cell,  156. 

spindle  cell,  156. 
Scarlet  fever,  326. 
Scharlach  R.,  30. 
Schistosomum  haematobium,  334. 
Schizogamy,  318. 
Scrotum,  teratoma,  192. 
Seminal  vesicles,  fasciculitis,  275. 
Septicaemia,  95. 
Sequestrum,  212. 
Skin,  hyperaemia,  326. 

lupus,  tuberculous  ulcer,  261. 

regeneration,  128. 

syphilis,  272. 

tuberculosis,  261. 

anatomical  ulcer,  261. 
Skull,  teratoma,  192. 
Smallpox,  320. 

balanitis,  322. 

confluent,  320. 

discrete,  320. 

purpura  variolosa,  320. 

pustulosa  haemorrhagica,  320. 

streptococcus  infection,  324. 
Sodium  urate,  40. 
Softening,  puriform,  64. 

purulent,  64. 
Spirilla,  195. 

Spirillum  cholerae  asiaticae,  309. 
Spleen,  congestion,  386. 
acute,  382. 


INDEX 


403 


Spleen,  continued. 
passive,  90. 

haemorrhage,  187. 

infarction,  97,  105,  187. 

leukaemia,  187. 

lymphoma  metastatic,  184. 

perisplenitis,  97,  100. 
chronic,  374. 

swelling,  acute,  105,  2ib,  227,  232, 

286,  299,  303,  310,  367. 
Splenic  fever,  285. 
Spores,  195. 
Sporozoite,  318. 

Staphylococcus  aureus,  105,  211,  213. 
Sternum,  erosion,  118,  212. 

carcinoma  metastatic,  179. 
Stomach,  carcinoma,  177. 

gastro-enterostomy,  179. 

ulcer,  365. 

Streptococcus,  95,  105,  217,  276,  292, 
326. 

septicaemia,  97,  263. 
Streptothrix  actinomyces,  280. 
Structure,  foam,  17. 
Susceptibility,  201. 
Symbiosis,  194. 
Syncitioma,  167. 
Synovitis,  239. 
Syphilis,  121,  271. 

amyloid  disease,  273. 

chancre,  271. 

congenital,  273. 

experiments,  275. 

secondary  infection  in,  273. 

vascular  lesions,  273. 

T. 
Taenia  echinococcus,  332, 

saginata,  331. 

solium,  331. 
Tapeworms,  331. 
Tattooing,  39. 
Teratoma,  167,  169. 

congenital,  192. 

scrotum,  192. 
Testicle,  necrosis  focal,  322. 

orchitis,  chronic,  275. 
Tetanus,  201. 

Thoracic  duct,  tuberculosis,  248,  263. 
Thrombus,  42,  63. 

canalization,  64. 


Thrombus,  continued. 

hyalin,  63. 

infection,  65. 

mural,  64. 

organization,  64. 

red,  63. 

tuberculous,  248. 

white,  63. 

Thrombophlebitis,  105,  310. 
Thrombosis,  62,    101,    108,    1 12,    121, 

189,  275- 
Thrush,  197. 
Tissue,  cicatricial,  57. 

connective,  21. 

fluid,  25. 
Tonsils,  diphtheria,  292. 

tonsilitis,  acute,  217. 

tuberculosis,  254. 
Toxins,  196. 
Trachea,  smallpox,  322. 

trachitis,  322. 

tuberculosis,  254. 
Treponema  pallid  urn,  271. 
Trichinella  spiralis,  194,  333. 
Tubercle,  conglomerate,  245. 

diffuse,  245. 

miliary,  244. 

structure,  245. 
Tuberculosis,  197,  200. 

aneurysm,  248. 

bacillus,  243. 

bile  ducts,  260. 

bladder,  257. 

bones,  260. 

brain,  259. 

caseation,  247. 

cicatrization,  246. 

conglomerate  tubercle,  245. 

diffuse  tuberculous  tissue,  245. 

disseminated,  partial,  249. 

exudate,  246. 

gcnitalia,  254. 

haemorrhage,  253. 

ilmm,  187. 

joints,  260. 

kidney,  256. 

larynx,  254. 

liver,  260. 

local,  249. 

lung,  249,  172,  176,  262. 
healed,  115. 


404 


INDEX 


Tuberculosis,  continued. 
meninges,  259. 
miliary,  acute,  263,  266. 
chronic,  249. 
disseminated,  249. 
general,  248. 
tubercle,  244. 

structure,  244. 
tuberculosis,  acute,  *6i. 
mode  of  infection,  243. 
mucous  membrane,  254. 
nephrophthisis,  256. 
phthisis,  252,  267. 
relation  of  tubercle  bacilli,  246. 
serous  surfaces,  258. 
skin,  261. 

anatomical  tubercle,  261. 
lesions  in  miliary  tuberculosis,  261. 
tuberculous  ulcer,  261. 
softening,  247. 
susceptibility,  244. 
thoracic  duct,  248. 
tissue  resistance,  244. 
tubercle,  solitary,  260. 
trachea,  254. 

tuberculous  bronchitis,  251. 
peribronchitis,  251. 
pneumonia,  251. 
thrombi,  248. 
ulcer,  254. 

primary,  187. 
ureter,  257. 
urinary  system,  256. 
Tumors,  131. 
adaptation,  139. 
adenoma,  145. 
aetiology,  145. 
angioma,  145. 
benign,  143. 
blood,  159. 

supply,  133. 
cachexia,  139. 
carcinoma,  145. 
cell  inclusions,  141. 
chloroma,  145. 
chondroma,  145. 
chorio  epithelioma,  145. 
classification,  143,  145. 
Cohnheim  theory,  143. 
cystic,  148. 
degeneration,  137. 


Tumors,  continued. 

embryoma,  145,  171. 

endothelioma,  145. 

environment,  139. 

epithelial,  162. 

experimental,  146,  193. 

nbro-epithelial,  150. 

fibroma,  145. 

frequency,  141. 

glioma,  145. 

hypernephroma,  145. 

immunity,  146. 

infection,  140. 

inheritance,  140. 

intercellular  substances,  133. 

leiomyoma,  145. 

leukocytoma,  145. 

lipoma,  145. 

lymphoma,  145. 

malignant,  143. 

melanoma,  145. 

metaplasia, '142. 

matastases,  135. 

mixed,  170. 

myeloma,  145. 

myoma,  145. 

myxoma,  145. 

necrosis,  137. 

neuroma,  145. 

of  animals,  146. 

origin,  133. 

osteoma,  145. 

papilloma,  145. 

rhabdomyoma,  145. 

sarcoma,  145. 

size,  131. 

structure,  132. 

teratoma,  145. 

thrombi,  135. 

tissue  changes,  134. 
Typhoid  fever,  298,  299,  303. 

endothelial  cell,  298. 

infection,  298. 

phagocytosis,  298. 

perforation  of  intestine,  303. 

ulceration  of  colon,  303. 

ulcer  of  pharynx,  303. 

U. 

Ulcer,  rodent,  166. 
Uncinaria  americana,  333. 


INDEX 


405 


Ureter,  double,  367. 

malformation,  341. 
Urethra,  smallpox,  322. 

stricture,  275. 

urethritis,  acute,  239. 

chronic,  275. 

Urinary  system,  tuberculosis,  256. 
Uterus,  myoma,  176. 

V. 

Vaccinia,  321. 
Variola,  320. 
Vasa  deferentia,  267. 
Veins,  76. 

thrombophlebitis,  105,  310. 

thrombi,  63. 
Vertebrae,  erosion,  120. 


Vesiculae  seminalcs,  tuberculosis,  255. 
Vessels,  blood,  20. 
lymphatics,  20. 
Virulence,  208. 

W. 

Wassermann  reaction,  275. 
Wool  sorter's  disease,  285. 
Worms,  parasitic,  331. 
tape,  331. 


Xanthoma,  152. 

i 

Yeasts,  195. 


X. 


Y. 


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